As director of both the Nainfec-tional Institute of Allergy and Infectious Diseases NIAID and the Office of AIDS Research at the National Institutes of Health NIH, Fauci is involved with
Trang 1Eye infections
the brain can also become infected Herpes Zoster eye
infec-tions can produce redness, swelling, pain, light sensitivity, and
blurred vision
The cornea of the eye is prone to infection by the type
of fungiknown as molds, and by yeast Such an infection is
termed mycotic keratitis Infections can arise following eye
surgery, from the use of contaminated contact lens (or the
contaminationof the contact lens cleaning solution), or due
to a malfunction of the immune system A common fungal
cause of eye infections are species of Aspergillus A common
yeast source of infection are species of Candida The eye
infection may be a secondary result of the spread of a fungal
or yeast infection elsewhere in the body For example, those
afflicted with acquired immunodeficiency syndrome candevelop eye infections in addition to other fungal or yeastmaladies
Bacterial eye infections are often caused by Chlamydia, Neiserria, and Pseudomonas The latter bacteria, which caninfect the fluid used to clean contact lenses, can cause therapid development of an infection that can so severe thatblindness can result Removal of the infected eye is sometimesnecessary to stop the infection
Less drastic solutions to infections include the use ofantimicrobial eye drops
See also Immune system
Trang 2Early in his career, Anthony S Fauci carried out both basic
and clinical research in immunology and infectious diseases
Since 1981, Fauci’s research has been focused on the
mecha-nisms of the Human Immunodeficiency Virus (HIV), which
causes acquired immunodeficiency syndrome (AIDS) His
work has lead to breakthroughs in understanding the virus’s
progress, especially during the latency period between
infec-tion and fulminant AIDS As director of both the Nainfec-tional
Institute of Allergy and Infectious Diseases (NIAID) and the
Office of AIDS Research at the National Institutes of Health
(NIH), Fauci is involved with much of the AIDS research
per-formed in the United States and is responsible for supervising
the investigation of the disease mechanism and the
develop-ment of vaccines and drug therapy
Anthony Stephen Fauci was born on December 24,
1940, in Brooklyn, New York, to Stephen A Fauci, a
pharma-cist, and Eugenia A Fauci, a homemaker He attended a Jesuit
high school in Manhattan where he had a successful academic
and athletic career After high school, Fauci entered Holy
Cross College in Worcester, Massachusetts, as a premedical
student, graduating with a B.A in 1962 He then attended
Cornell University Medical School, from which he received
his medical degree in 1966, and where he completed both his
internship and residency
In 1968, Fauci became a clinical associate in theLaboratory of Clinical Investigation of NIAID, one of the
eleven institutes that comprise the NIH Except for one year
spent at the New York Hospital Cornell Medical Center as
chief resident, he has remained at the NIH throughout his
career His earliest studies focused on the functioning of the
human immune systemand how infectious diseases impactthe system As a senior staff fellow at NIAID, Fauci and twoother researchers delineated the mechanism of Wegener’sgranulomatosis, a relatively rare and fatal immune diseaseinvolving the inflammationof blood vessels and organs By
1971, Fauci had developed a drug regimen for Wegener’sgranulomatosis that is 95% percent effective He also foundeffective treatments for lymphomatoid granulomatosis andpolyarteritis nodosa, two other immune diseases
In 1972, Fauci became a senior investigator at NIAIDand two years later he was named head of the ClinicalPhysiology Section In 1977, Fauci was appointed deputy clin-ical director of NIAID Fauci shifted the focus of theLaboratory of Clinical Infection at NIAID towards investigat-ing the nature of AIDS in the early 1980s It was in Fauci’s labthe type of defect that occurs in the T4 helper cells (theimmune cells) and enables AIDS to be fatal was demonstrated.Fauci also orchestrated early therapeutic techniques, includingbone-marrow transplants, in an attempt to save AIDS patients
In 1984, Fauci became the director of NIAID, and the ing year the coordinator of all AIDS research at NIH He hasworked not only against the disease but also against govern-mental indifference to AIDS, winning larger and larger budg-ets for AIDS research When the Office of AIDS Research atNIH was founded in 1988, Fauci was made director; he alsodecided to remain the director of NIAID Fauci and hisresearch teams have developed a three-fold battle plan againstAIDS: researching the mechanism of HIV, developing andtesting drug therapies, and creating an AIDS vaccine
follow-In 1993, Fauci and his team at NIH disproved the theorythat HIV remains dormant for approximately ten years after theinitial infection, showing instead that the virus attacks thelymph nodes and reproduces itself in white blood cells known
as CD4 cells This discovery could lead to new and radicalapproaches in the early treatment of HIV-positive patients.Earlier discoveries that Fauci and his lab are responsible forinclude the 1987 finding that a protein substance known ascytokine may be responsible for triggering full-blown AIDS
Trang 3Feldman, Harry Alfred • WORLD OF MICROBIOLOGY AND IMMUNOLOGY
and the realization that the macrophage, a type of immune
sys-tem cell, is the virus’s means of transmission Fauci
demon-strated that HIV actually hides from the body’s immune system
in these macrophages and is thus more easily transmitted In an
interview with Dennis L Breo published in the Journal of the
American Medical Association, Fauci summed up his research
to date: “We’ve learned that AIDS is a multiphasic,
multifacto-rial disease of overlapping phases, progressing from infection
to viral replication to chronic smoldering disease to profound
depression of the immune system.”
In drug therapy work, Fauci and his laboratory have runhundreds of clinical tests on medications such as azidothymi-
dine (AZT), and Fauci has pushed for the early use of such
drugs by terminally ill AIDS patients Though no completely
effective antiviral drug yet exists, drug therapies have been
developed that can prolong the life of AIDS victims Potential
AIDS vaccines are still being investigated, a process
compli-cated by the difficulty of conducting possible clinical trials,
and the fact that animals do not develop AIDS as humans do,
which further limits available research subjects No viable
vaccine is expected before the year 2005
As chief government infectious disease specialist, Fauciwas presented with an immediate public health challenge in
October, 2001—bioterrorism Coordinating with the Centers
contain the outbreak of anthrax resulting from Bacillus
anthracis–contaminated letters mailed to United States Post
Offices, but also to initiate the necessary research to manage
the continuing threat of the disease Fauci also labeled
small-poxas a logical bioterrorismagent, and has concentrated his
efforts to ensure an available adequate supply of smallpox
vac-cine in the U.S
Fauci married Christine Grady, a clinical nurse andmedical ethicist, in 1985 The couple has three daughters
Fauci is an avid jogger, a former marathon runner, and enjoys
fishing Widely recognized for his research, he is the recipient
of numerous prizes and awards, including a 1979 Arthur S
Flemming Award, the 1984 U.S Public Health Service
Distinguished Service Medal, the 1989 National Medical
Research Award from the National Health Council, and the
1992 Dr Nathan Davis Award for Outstanding Public Service
from the American Medical Association Fauci is also a fellow
of the American Academy of Arts and Sciences and holds a
number of honorary degrees He is the author or coauthor of
over 800 scientific articles, and has edited several medical
textbooks
See also AIDS, recent advances in research and treatment;
Anthrax, terrorist use of as a biological weapon; Bioterrorism,
protective measures; Epidemiology, tracking diseases with
technology; Infection and resistance
F ELDMAN , H ARRY A LFRED (1914-1985)
Feldman, Harry Alfred
American physician and epidemiologist
Harry A Feldman’s research in epidemiology, immunology,
infectious disease control, preventive medicine, toxoplasmosis,
bacterial chemotherapeutic and sero-therapeutic agents, tory diseases, and meningitiswas internationally recognized inthe scientific community of microbiology and medicine.Feldman was born in Newark, New Jersey on May, 30,
respira-1914, the son of Joseph Feldman, a construction contractor,and his wife Sarah After attending public schools in Newarkand graduating from Weequahic High School in 1931, hereceived his A.B in zoology in 1935 and his M.D in 1939,both from George Washington University He completed aninternship and residency at Gallinger Municipal Hospital,Washington, D.C., held a brief research fellowship at GeorgeWashington, then in 1942, became a research fellow atHarvard Medical School and an assistant resident physician atthe Boston City Hospital’s Thorndike Memorial Laboratory.Among his colleagues at Thorndike was Maxwell A Finland(1902–1987), who at the time was among the nation’s premierinvestigators of infectious diseases From 1942 to 1946,Feldman served to the rank of lieutenant colonel in the UnitedStates Army Medical Corps
As senior fellow in virus diseases for the NationalResearch Council at the Children’s Hospital ResearchFoundation, Cincinnati, Ohio, Feldman collaborated withAlbert B Sabin (1906–1993) on poliomyelitis and toxoplas-mosis from 1946 to 1948 Together they developed the Sabin-Feldman dye test, which uses methylene blue to detecttoxoplasmosis in blood serum by identifying immunoglobu-lin-G (IgG) antibodies against the parasitic intracellular proto-
zoan, toxoplasma gondii.
In 1948, Feldman was appointed associate professor ofmedicine at the Syracuse University College of Medicine,which in 1950 became the State University of New YorkUpstate Medical Center College of Medicine From 1949 to
1956, he also served in Syracuse as director of research at theWieting-Johnson Hospital for Rheumatic Diseases In 1955,Upstate named him associate professor of preventive medi-cine The following year he was promoted to full professorand in 1957, became chair of the Department of PreventiveMedicine, the position he held until his death Between 1938and 1983, he published 216 research papers, both in scientificjournals and as book chapters With Alfred S Evans (1917-
1996), he co-edited Bacterial Infections of Humans (1982).
Besides his groundbreaking work on toxoplasmosis,both with Sabin in Cincinnati and later as head of his ownteam in Syracuse, Feldman regarded his work on meningo-coccus and on parasitic protozoasuch as acanthamoeba as hisgreatest contributions to science Among the diseases he stud-ied were malaria, pneumonia, rubella, measles, influenza,streptococcal infections, and AIDS He conducted extensiveclinical pharmaceutical trials and served enthusiastically as amember of many scientific organizations, commissions, andcommittees, including the World Health Organization (WHO)expert advisory panels on bacterial diseases, venereal dis-eases, treponematoses, and neisseria infections He was presi-dent of the American Epidemiological Society (AES), theInfectious Diseases Society of America (IDSA), and theAssociation of Teachers of Preventive Medicine The AESestablished the Harry A Feldman Lectureship and the Harry
Trang 4A Feldman Award in his honor, and the IDSA also created its
own Harry A Feldman Award
See also Antibody and antigen; Bacteria and bacterial
infec-tion; Chemotherapy; Epidemiology; Infection and resistance;
Meningitis, bacterial and viral; Microbiology, clinical;
Parasites; Poliomyelitis and polio; Protozoa; Serology
FERMENTATION
Fermentation
In its broadest sense, fermentation refers to any process by
which large organic molecules are broken down to simpler
molecules as the result of the action of microorganisms The
most familiar type of fermentation is the conversion of sugars
and starches to alcohol by enzymesin yeast To distinguish
this reaction from other kinds of fermentation, the process is
sometimes known as alcoholic or ethanolic fermentation
Ethanolic fermentation was one of the first chemicalreactions observed by humans In nature, various types of
spoil decompose because of bacterial action Early in history,
humans discovered that this kind of change could result in the
formation of products that were enjoyable to consume The
spoilage (fermentation) of fruit juices, for example, resulted in
the formation of primitive forms of wine
The mechanism by which fermentation occurs was thesubject of extensive debate in the early 1800s It was a key
issue among those arguing over the concept of vitalism, the
notion that living organisms are in some way inherently
dif-ferent from non-living objects One aspect in this debate
cen-tered on the role of so-called “ferments” in the conversion of
sugars and starches to alcohol Vitalists argued that ferments
(now known as enzymes) are inextricably linked to a living
cell; destroy a cell and ferments can no longer cause
fermen-tation, they argued
A crucial experiment on this issue was carried out in
1896 by the German chemist Eduard Buchner Buchner
ground up a group of cells with sand until they were totally
destroyed He then extracted the liquid that remained and
added it to a sugar solution His assumption was that
fermen-tation could no longer occur because the cells that had held the
ferments were dead, so they no longer carried the “life-force”
needed to bring about fermentation He was amazed to
dis-cover that the cell-free liquid did indeed cause fermentation It
was obvious that the ferments themselves, distinct from any
living organism, could cause fermentation
The chemical reaction that occurs in fermentation can
be described easily Starch is converted to simple sugars such
as sucrose and glucose Those sugars are then converted to
alcohol (ethyl alcohol) and carbon dioxide This description
does not adequately convey the complexity of the
fermenta-tion process itself During the 1930s, two German
bio-chemists, G Embden and O Meyerhof, worked out the
sequence of reactions by which glucose ferments In a
sequence of twelve reactions, glucose is converted to ethyl
alcohol and carbon dioxide A number of enzymes are needed
to carry out this sequence of reactions, the most important of
which is zymase, found in yeast cells These enzymes are
sen-sitive to environmental conditions in which they live Whenthe concentration of alcohol reaches about 14%, they are inac-tivated For this reason, no fermentation product (such aswine) can have an alcoholic concentration of more than aboutfourteen percent
The alcoholic beverages that can be produced by mentation vary widely, depending primarily on two factors—the plant that is fermented and the enzymes used forfermentation Human societies use, of course, the materialsthat are available to them Thus, various peoples have usedgrapes, berries, corn, rice, wheat, honey, potatoes, barley,hops, cactus juice, cassava roots, and other plant materials forfermentation The products of such reactions are various forms
fer-of beer, wine or distilled liquors, which may be given specificnames depending on the source from which they come InJapan, for example, rice wine is known as sake Wine preparedfrom honey is known as mead Beer is the fermentation prod-uct of barley, hops, and/or malt sugar
Early in human history, people used naturally occurringyeast for fermentation The products of such reactions
Large vats in which the fermentation process in the brewing of beer occurs.
Trang 5Fleming, Alexander • WORLD OF MICROBIOLOGY AND IMMUNOLOGY
depended on whatever enzymes might occur in “wild” yeast
Today, wine-makers are able to select from a variety of
spe-cially cultured yeast that control the precise direction that
fer-mentation will take
Ethyl alcohol is not the only useful product of tation The carbon dioxide generated during fermentation is
fermen-also an important component of many baked goods When the
batter for bread is mixed, for example, a small amount of sugar
and yeast is added During the rising period, sugar is
fer-mented by enzymes in the yeast, with the formation of carbon
dioxide gas The carbon dioxide gives the batter bulkiness and
texture that would be lacking without the fermentation
process Fermentation has a number of commercial
applica-tions beyond those described thus far Many occur in the food
preparation and processing industry A variety of bacteriaare
used in the production of olives, cucumber pickles, and
sauer-kraut from the raw olives, cucumbers, and cabbage,
respec-tively The selectionof exactly the right bacteria and the right
conditions (for example, acidity and salt concentration) is an
art in producing food products with exactly the desired
fla-vors An interesting line of research in the food sciences is
aimed at the production of edible food products by the
fer-mentation of petroleum
In some cases, antibioticsand other drugs can be pared by fermentation if no other commercially efficient
pre-method is available For example, the important drug
corti-sone can be prepared by the fermentation of a plant steroid
known as diosgenin The enzymes used in the reaction are
pro-vided by the moldRhizopus nigricans.
One of the most successful commercial applications offermentation has been the production of ethyl alcohol for use
in gasohol Gasohol is a mixture of about 90% gasoline and
10% alcohol The alcohol needed for this product can be
obtained from the fermentation of agricultural and municipal
wastes The use of gasohol provides a promising method for
using renewable resources (plant material) to extend the
avail-ability of a nonrenewable resource (gasoline)
Another application of the fermentation process is in thetreatment of wastewater In the activated sludge process, aerobic
bacteria are used to ferment organic material in wastewater Solid
wastes are converted to carbon dioxide, water, and mineral salts
See also History of microbiology; Winemaking
FERTILITY • see REPRODUCTIVE IMMUNOLOGY
FILOVIRUSES • see HEMORRHAGIC FEVERS AND
DISEASES
FIMBRIA • see BACTERIAL APPENDAGES
FLAGELLA • see BACTERIAL APPENDAGES
FLAVIVIRUSES • see HEMORRHAGIC FEVERS AND DIS
Fleming was born in 1881 to a farming family inLochfield, Scotland Following school, he worked as a ship-ping clerk in London and enlisted in the London ScottishRegiment In 1901, he began his medical career, entering St.Mary’s Hospital Medical School, where he was a prizewin-ning student After graduation in 1906, he began working atthat institution with Sir Almroth Edward Wright, a pathologist.From the start, Fleming was innovative and became one of thefirst to use Paul Ehrlich’s arsenic compound, Salvarsan, totreat syphilisin Great Britain
Wright and Fleming joined the Royal Army MedicalCorps during World War I and they studied wounds and infec-tion-causing bacteriaat a hospital in Boulogne, France At thattime, antisepticswere used to treat bacterial infections, butWright and Fleming showed that, especially in deep wounds,bacteria survive treatment by antiseptics while the protectivewhite blood cells in the wound are destroyed This creates aneven worse situation in which infection can spread rapidly.Forever affected by the suffering he saw during the war,Fleming decided to focus his efforts on the search for safeantibacterial substances He studied the antibacterial power ofthe body’s own leukocytes contained in pus In 1921, he dis-covered that a sample of his own nasal mucus destroyed bac-teria in a petri dish He isolated the compound responsible forthe antibacterial action, which he called lysozyme, in saliva,blood, tears, pus, milk, and in egg whites
Fleming made his greatest discovery in 1928 While hewas growing cultures of bacteria in petri dishes for experi-ments, he accidentally left certain dishes uncovered for severaldays Fleming found a moldgrowing in the dishes and began
to discard them, when he noticed, to his astonishment, thatbacteria near the molds were being destroyed He preservedthe mold, a strain of Penicillium and made a cultureof it in atest tube for further investigation He deduced an antibacterialcompound was being produced by the mold, and named itpenicillin Through further study, Fleming found that peni-cillin was nontoxic in laboratory animals He described hisfindings in research journals but was unable to purify and con-centrate the substance Little did he realize that the substanceproduced by his mold would save millions of lives during thetwentieth century
Fleming dropped his investigation of penicillin and hisdiscovery remained unnoticed until 1940 It was then thatOxford University-based bacteriologists Howard Florey andErnst Chain stumbled upon a paper by Fleming whileresearching antibacterial agents They had better fortune thanFleming, for they were able to purify penicillin and test it onhumans with outstanding results During World War II, thedrug was rushed into mass-production in England and theUnited States and saved thousands of injured soldiers frominfections that might otherwise have been fatal
Trang 6Florey, Howard Walter
Accolades followed for Fleming He was elected to lowship in the Royal Society in 1943, knighted in 1944, and
fel-shared the Nobel Prize with Florey and Chain in 1945
Fleming continued working at St Mary’s Hospital until 1948,
when he moved to the Wright-Fleming Institute Fleming died
in London in 1955
See also Antibiotic resistance, tests for; Antibiotics; Bacteria
and bacterial infection; History of the development of
antibi-otics; History of microbiology; History of public health
Florey, Howard Walter
English pathologist
The work of Howard Walter Florey gave the world one of its
most valuable disease-fighting drugs, penicillin Alexander
anti-bacterial substance, but was unable to isolate it Nearly a
decade later, Florey and his colleague, biochemist Ernst
mold and then conduct the clinical tests that demonstrated
penicillin’s remarkable therapeutic value Florey and Chain
reported the initial success of their clinical trials in 1940, and
the drug’s value was quickly recognized In 1945, Florey
shared the Nobel Prize in medicine or physiology withFleming and Chain
Howard Walter Florey was born in Adelaide, Australia
He was one of three children and the only son born to JosephFlorey, a boot manufacturer, and Bertha Mary Wadham Florey,Joseph’s second wife Florey expressed an interest in scienceearly in life Rather than follow his father’s career path, hedecided to pursue a degree in medicine Scholarships affordedhim an education at St Peter’s Collegiate School and AdelaideUniversity, the latter of which awarded him a Bachelor ofScience degree in 1921 An impressive academic careerearned Florey a Rhodes scholarship to Oxford University inEngland There he enrolled in Magdalen College in January
1922 His academic prowess continued at Oxford, where hebecame an excellent student of physiology under the tutelage
of renowned neurophysiologist Sir Charles Scott Sherrington.Placing first in his class in the physiology examination, he wasappointed to a teaching position by Sherrington in 1923.Florey’s education continued at Cambridge University
as a John Lucas Walker Student Already fortunate enough tohave learned under a master such as Sherrington, he now cameunder the influence of Sir Frederick Gowland Hopkins, whotaught Florey the importance of studying biochemical reac-tions in cells A Rockefeller Traveling Scholarship sent Florey
to the United States in 1925, to work with physiologist AlfredNewton Richards at the University of Pennsylvania, a collab-oration that would later prove beneficial to Florey’s ownresearch On his return to England and Cambridge in 1926,Florey received a research fellowship in pathology at LondonHospital That same year, he married Mary Ethel Hayter Reed,
an Australian whom he’d met during medical school atAdelaide University The couple eventually had two children.Florey received his Ph.D from Cambridge in 1927, andremained there as Huddersfield Lecturer in Special Pathology.Equipped with a firm background in physiology, he was now
in a position to pursue experimental research using anapproach new to the field of pathology Instead of describingdiseased tissues and organs, Florey applied physiologic con-cepts to the study of healthy biological systems as a means ofbetter recognizing the nature of disease It was during thisperiod in which Florey first became familiar with the work ofAlexander Fleming His own work on mucus secretion led him
to investigate the intestine’s resistance to bacterial infection
As he became more engrossed in antibacterial substances,Florey came across Fleming’s report of 1921 describing theenzyme lysozyme, which possessed antibacterial properties.The enzyme, found in the tears, nasal secretions, and saliva ofhumans, piqued Florey’s interest, and convinced him that col-laboration with a chemist would benefit his research His workwith lysozyme showed that extracts from natural substances,such as plants, fungiand certain types of bacteria, had the abil-ity to destroy harmful bacteria
Florey left Cambridge in 1931 to become professor ofpathology at the University of Sheffield, returning to Oxford
in 1935 as director of the new Sir William Dunn School ofPathology There, at the recommendation of Hopkins, his pro-ductive collaboration began with the German biochemist ErnstChain Florey remained interested in antibacterial substances
Sir Alexander Flemming, the discoverer of lysozyme and penicillin.
Trang 7Flu: The great flu epidemic of 1918 • WORLD OF MICROBIOLOGY AND IMMUNOLOGY
even as he expanded his research projects into new areas, such
as cancer studies During the mid 1930s, sulfonamides, or
streptococcal infections, an announcement which boosted
Florey’s interest in the field At Florey’s suggestion, Chain
undertook biochemical studies of lysozyme He read much of
the scientific literature on antibacterial substances, including
Fleming’s 1929 report on the antibacterial properties of a
sub-stance extracted from a Penicillium mold, which he called
penicillin Chain discovered that lysozyme acted against
cer-tain bacteria by catalyzing the breakdown of polysaccharides
in them, and thought that penicillin might also be an enzyme
with the ability to disrupt some bacterial component Chain
and Florey began to study this hypothesis, with Chain
concen-trating on isolating and characterizing the enzyme, and Florey
studying its biological properties
To his surprise, Chain discovered that penicillin was not
a protein, therefore it could not be an enzyme His challenge
now was to determine the chemical nature of penicillin, made
all the more difficult because it was so unstable in the
labora-tory It was, in part, for this very reason that Fleming
eventu-ally abandoned a focused pursuit of the active ingredient in
Penicillium mold Eventually, work by Chain and others led to
a protocol for keeping penicillin stable in solution By the end
of 1938, Florey began to seek funds to support more vigorous
research into penicillin He was becoming convinced that this
antibacterial substance could have great practical clinical
value Florey was successful in obtaining two major grants,
one from the Medical Research Council in England, the other
from the Rockefeller Foundation in the United States
By March of 1940, Chain had finally isolated about onehundred milligrams of penicillin from broth cultures
Employing a freeze-drying technique, he extracted the
yel-lowish-brown powder in a form that was yet only ten percent
pure It was non-toxic when injected into mice and retained
antibacterial properties against many different pathogens In
May of 1940, Florey conducted an important experiment to
test this promising new drug He infected eight mice with
lethal doses of streptococcibacteria, then treated four of them
with penicillin The following day, the four untreated mice
were dead, while three of the four mice treated with penicillin
had survived Though one of the mice that had been given a
smaller dose died two days later, Florey showed that penicillin
had excellent prospects, and began additional tests In 1941,
enough penicillin had been produced to run the first clinical
trial on humans Patients suffering from severe staphylococcal
and streptococcal infections recovered at a remarkable rate,
bearing out the earlier success of the drugs in animals At the
outset of World War II, however, the facilities needed to
pro-duce large quantities of penicillin were not available Florey
went to the United States where, with the help of his former
colleague, Alfred Richards, he was able to arrange for a U.S
government lab to begin large-scale penicillin production By
1943, penicillin was being used to treat infections suffered by
wounded soldiers on the battlefront
Recognition for Florey’s work came quickly In 1942,
he was elected a fellow in the prestigious British scientific
organization, the Royal Society, even before the importance of
penicillin was fully realized Two years later, Florey wasknighted In 1945, Florey, Chain and Fleming shared theNobel Prize in medicine or physiology for the discovery ofpenicillin
Penicillin prevents bacteria from synthesizing intact cellwalls Without the rigid, protective cell wall, a bacterium usu-ally bursts and dies Penicillin does not kill resting bacteria,only prevents their proliferation Penicillin is active againstmany of the gram positive and a few gram negative bacteria.(The gram negative/positive designation refers to a stainingtechnique used in identification of microbes.) Penicillin hasbeen used in the treatment of pneumonia, meningitis, manythroat and ear infections, Scarlet Fever, endocarditis (heartinfection), gonorrhea, and syphilis
Following his work with penicillin, Florey retained aninterest in antibacterial substances, including thecephalosporins, a group of drugs that produced effects similar
to penicillin He also returned to his study of capillaries, which
he had begun under Sherrington, but would now be aided bythe recently developed electron microscope Florey remainedinterested in Australia, as well In 1944, the prime minister ofAustralia asked Florey to conduct a review of the country’smedical research During his trip, Florey found laboratoriesand research facilities to be far below the quality he expected.The trip inspired efforts to establish graduate-level researchprograms at the Australian National University For a while, itlooked as if Florey might even return to Australia to head anew medical institute at the University That never occurred,although Florey did do much to help plan the institute andrecruit scientists to it During the late 1940s and 1950s, Floreymade trips almost every year to Australia to provide consulta-tion to the new Australian National University, to which hewas appointed Chancellor in 1965
Florey’s stature as a scientist earned him many honors
in addition to the Nobel Prize In 1960, he became president ofthe Royal Society, a position he held until 1965 Tapping hisexperience as an administrator, Florey invigorated this presti-gious scientific organization by boosting its membership andincreasing its role in society In 1962, he was elected Provost
of Queen’s College, Oxford University, the first scientist tohold that position He accepted the presidency of the BritishFamily Planning Association in 1965, and used the post to pro-mote more research on contraception and the legalization ofabortion That same year, he was granted a peerage, becomingBaron Florey of Adelaide and Marston
See also Bacteria and bacterial infection; History of the
devel-opment of antibiotics; Infection and resistance
FLU: THE GREAT FLU EPIDEMIC OF 1918
Flu: The great flu epidemic of 1918
From 1918 to 1919, an outbreak of influenzaravaged Europeand North America The outbreak was a pandemic; that is,individuals in a vast geographic area were affected In the case
Trang 8Fluorescence in situ hybridization (FISH)
of this particular influenza outbreak, people were infected
around the world
The pandemic killed more people, some 20 to 40 lion, than had been killed in the just-ending Great War (now
mil-known as World War I) Indeed, the pandemic is still the most
devastating microbiological event in the recorded history of
the world At the height of the epidemic, fully one-fifth of the
world’s population was infected with the virus
The disease first arose in the fall of 1918, as World War
I was nearing its end The genesis of the disease caused by the
strain of influenza virus may have been the deplorable
condi-tions experienced by soldiers in the trenches that were dug at
battlegrounds throughout Europe The horrible conditions
ren-dered many soldiers weak and immunologically impaired As
solders returned to their home countries, such as the United
States, the disease began to spread As the disease spread,
however, even healthy people fell victim to the infection The
reason why so many apparently healthy people would
sud-denly become ill and even die was unknown at the time
Indeed, the viral cause of disease had yet to be discovered
Recent research has demonstrated that the particularstrain of virus was one that even an efficiently functioning
muta-tion produced a surface protein on the virus that was not
immediately recognized by the immune system, and which
contributed to the ability of the virus to cause an infection
The influenza outbreak has also been called the
“Spanish Flu” or “La Grippe.” The moniker came from the
some 8 million influenza deaths that occurred in Spain in one
month at the height of the outbreak Ironically, more recent
research has demonstrated that the strain of influenza that
rav-aged Spain was different from that which spread influenza
around the world
The influenza swept across Europe and elsewherearound the globe In the United States, some 675,000
Americans perished from the infection, which was brought to
the continent by returning war veterans The outbreaks in the
United States began in military camps Unfortunately, the
sig-nificance of the illness was not recognized by authorities and
few steps were taken to curtail the illnesses, which soon
spread to the general population
The resulting carnage in the United States reduced thestatistical average life span of an American by 10 years In the
age range of 15 to 34 years, the death rate in 1918 due to
The large number of deaths in many of the young generation
had an economic effect for decades to come South America,
Asia, and the South Pacific were also devastated by the
infec-tion
In the United States the influenza outbreak greatlyaffected daily life Gatherings of people, such as at funerals,
parades, or even sales at commercial establishments were
either banned or were of very short duration The medical
sys-tem was taxed tremendously
The influenza outbreak of 1918 was characterized by ahigh mortality rate Previous influenza outbreaks had displayed
a mortality rate of far less than 1% However, the 1918
pan-demic had a much higher mortality rate of 2.5% Also, the
ill-ness progressed very quickly once the symptoms of infectionsappeared In many cases, an individual went from a healthystate to serious illness or death with 24 hours
At the time of the outbreak, the case of the illness wasnot known Speculations as to the source of the illnessincluded an unknown weapon of war unleashed by theGerman army Only later was the viral origin of the diseasedetermined In the 1970s, a study that involved a genetic char-acterization of viral material recovered from the time of thepandemic indicated that the strain of the influenza virus likelyarose in China, and represented a substantial genetic alterationfrom hitherto known viral types
In November of 1919, the influenza outbreak began todisappear as rapidly as it had appeared With the hindsight ofpresent day knowledge of viral epidemics, it is clear that thenumber of susceptible hosts for the virus became exhausted.The result was the rapid end to the epidemic
See also Epidemics, viral; History of public health
FLUORESCENCE IN SITU HYBRIDIZATION (FISH)
Fluorescence in situ hybridization (FISH)
Fluorescent in situ hybridization (FISH) is a technique in
which single-stranded nucleic acids (usually DNA, but RNA
may also be used) are permitted to interact so that complexes,
or hybrids, are formed by molecules with sufficiently similar,complementary sequences Through nucleic acid hybridiza-tion, the degree of sequence identity can be determined, andspecific sequences can be detected and located on a givenchromosome It is a powerful technique for detecting RNA orDNA sequences in cells, tissues, and tumors FISH provides aunique link among the studies of cell biology, cytogenetics,
The method is comprised of three basic steps: fixation
of a specimen on a microscopeslide, hybridization of labeledprobe to homologous fragments of genomic DNA, and enzy-matic detection of the tagged probe-target hybrids Whileprobe sequences were initially detected with isotopic reagents,nonisotopic hybridization has become increasingly popular,with fluorescent hybridization now a common choice.Protocols involving nonisotopic probes are considerablyfaster, with greater signal resolution, and provide options tovisualize different targets simultaneously by combining vari-ous detection methods
The detection of sequences on the target chromosomes
is performed indirectly, commonly with biotinylated or igenin-labeled probes detected via a fluorochrome-conjugateddetection reagent, such as an antibodyconjugated with fluo-rescein As a result, the direct visualization of the relative posi-tion of the probes is possible Increasingly, nucleic acid probeslabeled directly with fluorochromes are used for the detection
digox-of large target sequences This method takes less time andresults in lower background; however, lower signal intensity isgenerated Higher sensitivity can be obtained by building lay-ers of detection reagents, resulting in amplification of the sig-
Trang 9Fluorescent dyes • WORLD OF MICROBIOLOGY AND IMMUNOLOGY
nal Using such means, it is possible to detect single-copy
sequences on chromosome with probes shorter than 0.8 kb
Probes can vary in length from a few base pairs for thetic oligonucleotides to larger than one Mbp Probes of dif-
syn-ferent types can be used to detect distinct DNA types
PCR-amplified repeated DNA sequences, oligonucleotides
specific for repeat elements, or cloned repeat elements can be
used to detect clusters of repetitive DNA in heterochromatin
blocks or centromeric regions of individual chromosomes
These are useful in determining aberrations in the number of
chromosomes present in a cell In contrast, for detecting
sin-gle locus targets, cDNAs or pieces of cloned genomic DNA,
from 100 bp to 1 Mbp in size, can be used
To detect specific chromosomes or chromosomal regions,chromosome-specific DNA libraries can be used as probes to
delineate individual chromosomes from the full chromosomal
for each of the human chromosomes since 1991
Any given tissue or cell source, such as sections offrozen tumors, imprinted cells, cultured cells, or embedded
sections, may be hybridized The DNA probes are hybridized
to chromosomes from dividing (metaphase) or non-dividing
(interphase) cells
The observation of the hybridized sequences is doneusing epifluorescence microscopy White light from a source
lamp is filtered so that only the relevant wavelengths for
excita-tion of the fluorescent molecules reach the sample The light
emitted by fluorochromes is generally of larger wavelengths,
which allows the distinction between excitation and emission
light by means of a second optical filter Therefore, it is
possi-ble to see bright-colored signals on a dark background It is also
possible to distinguish between several excitation and emission
bands, thus between several fluorochromes, which allows the
observation of many different probes on the same target
FISH has a large number of applications in molecular
diag-nosis of chromosomal abnormalities, and studies of cellular
structure and function Chromosomes in three-dimensionally
preserved nuclei can be “painted” using FISH In clinical
research, FISH can be used for prenatal diagnosis of inherited
chromosomal aberrations, postnatal diagnosis of carriers of
genetic disease, diagnosis of infectious disease, viral and
bac-terial disease, tumor cytogenetic diagnosis, and detection of
aberrant gene expression In laboratory research, FISH can be
used for mapping chromosomal genes, to study the evolution
of genomes (Zoo FISH), analyzing nuclear organization,
visu-alization of chromosomal territories and chromatin in
inter-phase cells, to analyze dynamic nuclear processes, somatic
hybrid cells, replication, chromosome sorting, and to study
tumor biology It can also be used in developmental biology to
study the temporal expression of genes during differentiation
and development Recently, high resolution FISH has become
a popular method for ordering genes or DNA markers within
chromosomal regions of interest
See also Biochemical analysis techniques; Biotechnology;
Laboratory techniques in immunology; Laboratory techniques
in microbiology; Molecular biology and molecular genetics
MICROSCOPE AND MICROSCOPY
FLUORESCENT DYES
Fluorescent dyes
The use of fluorescent dyes is the most popular tool for uring ion properties in living cells Calcium, magnesium,sodium, and similar species that do not naturally fluoresce can
meas-be measured indirectly by complexing them with fluorescentmolecules The use of probes, which fluoresce at one wave-length when unbound, and at a different wavelength whenbound to an ion, allows the quantification of the ion level.Fluorescence has also become popular as an alternative
to radiolabeling of peptides Whereas labeling of peptides with
a radioactive compound relies on the introduction of a labeled amino acid as part of the natural structure of the pep-tide, fluorescent tags are introduced as an additional group tothe molecule
radio-The use of fluorescent dyes allows the detection ofminute amounts of the target molecule within a mixture ofmany other molecules In combination with light microscopictechniques like confocal laser microscopy, the use of fluores-cent dyes allows three-dimensional image constructs to becomplied, to provide precise spatial information on the targetlocation Finally, fluorescence can be used to gain informationabout phenomena such as blood flow and organelle movement
in real time
The basis of fluorescent dyes relies on the absorption oflight at a specific wavelength and, in turn, the excitation of theelectrons in the dye to higher energy levels As the electronsfall back to their lower pre-excited energy levels, they re-emitlight at longer wavelengths and so at lower energy levels Thelower-energy light emissions are called spectral shifts Theprocess can be repeated
Proper use of a fluorescent dye requires 1) that its usedoes not alter the shape or function of the target cell, 2) thatthe dye localizes at the desired location within or on the cell,3) that the dye maintains its specificity in the presence of com-peting molecules, and 4) that they operate at near visiblewavelengths Although none of the dyes in use today meets all
of these criteria, fluorescent dyes are still useful for stainingand observation to a considerable degree
See also Biochemical analysis techniques; Biotechnology;
Electron microscope, transmission and scanning; Electronmicroscopic examination of microorganisms; Immunofluores-cence; Microscope and microscopy
FOOD PRESERVATION
Food preservation
The term food preservation refers to any one of a number oftechniques used to prevent food from spoiling It includesmethods such as canning, pickling, drying and freeze-drying,irradiation, pasteurization, smoking, and the addition of chem-ical additives Food preservation has become an increasingly
Trang 10Food preservation
important component of the food industry as fewer people eat
foods produced on their own lands, and as consumers expect to
be able to purchase and consume foods that are out of season
The vast majority of instances of food spoilage can beattributed to one of two major causes: (1) the attack by
pathogens (disease-causing microorganisms) such as bacteria
and molds, or (2) oxidation that causes the destruction of
essential biochemical compounds and/or the destruction of
plant and animal cells The various methods that have been
devised for preserving foods are all designed to reduce or
eliminate one or the other (or both) of these causative agents
For example, a simple and common method of ing food is by heating it to some minimum temperature This
preserv-process prevents or retards spoilage because high
tempera-tures kill or inactivate most kinds of pathogens The addition
of compounds known as BHA and BHT to foods also prevents
spoilage in another different way These compounds are
known to act as antioxidants, preventing chemical reactions
that cause the oxidation of food that results in its spoilage
Almost all techniques of preservation are designed to extend
the life of food by acting in one of these two ways
The search for methods of food preservation probablycan be traced to the dawn of human civilization People who
lived through harsh winters found it necessary to find some
means of insuring a food supply during seasons when no fresh
fruits and vegetables were available Evidence for the use of
dehydration (drying) as a method of food preservation, for
example, goes back at least 5,000 years Among the most
primitive forms of food preservation that are still in use today
are such methods as smoking, drying, salting, freezing, and
fermenting
Early humans probably discovered by accident that tain foods exposed to smoke seem to last longer than those that
cer-are not Meats, fish, fowl, and cheese were among such foods
It appears that compounds present in wood smoke have
anti-microbial actions that prevent the growth of organisms that
cause spoilage Today, the process of smoking has become a
sophisticated method of food preservation with both hot and
cold forms in use Hot smoking is used primarily with fresh or
frozen foods, while cold smoking is used most often with salted
products The most advantageous conditions for each kind of
smoking—air velocity, relative humidity, length of exposure,
and salt content, for example—are now generally understood
and applied during the smoking process For example,
electro-static precipitators can be employed to attract smoke particles
and improve the penetration of the particles into meat or fish
So many alternative forms of preservation are now available
that smoking no longer holds the position of importance it once
did with ancient peoples More frequently, the process is used
to add interesting and distinctive flavors to foods
Because most disease-causing organisms require amoist environment in which to survive and multiply, drying is
a natural technique for preventing spoilage Indeed, the act of
simply leaving foods out in the sun and wind to dry out is
probably one of the earliest forms of food preservation
Evidence for the drying of meats, fish, fruits, and vegetables
go back to the earliest recorded human history At some point,
humans also learned that the drying process could be hastened
and improved by various mechanical techniques For example,the Arabs learned early on that apricots could be preservedalmost indefinitely by macerating them, boiling them, andthen leaving them to dry on broad sheets The product of thistechnique, quamaradeen, is still made by the same process inmodern Muslim countries
Today, a host of dehydrating techniques are known andused The specific technique adopted depends on the proper-ties of the food being preserved For example, a traditionalmethod for preserving rice is to allow it to dry naturally in thefields or on drying racks in barns for about two weeks Afterthis period of time, the native rice is threshed and then driedagain by allowing it to sit on straw mats in the sun for aboutthree days Modern drying techniques make use of fans andheaters in controlled environments Such methods avoid theuncertainties that arise from leaving crops in the field to dryunder natural conditions Controlled temperature air drying isespecially popular for the preservation of grains such asmaize, barley, and bulgur
Vacuum drying is a form of preservation in which afood is placed in a large container from which air is removed.Water vapor pressure within the food is greater than that out-side of it, and water evaporates more quickly from the foodthan in a normal atmosphere Vacuum drying is biologicallydesirable since some enzymesthat cause oxidation of foodsbecome active during normal air drying These enzymes donot appear to be as active under vacuum drying conditions,however Two of the special advantages of vacuum drying arethat the process is more efficient at removing water from afood product, and it takes place more quickly than air drying
In one study, for example, the drying time of a fish fillet wasreduced from about 16 hours by air drying to six hours as aresult of vacuum drying
Coffee drinkers are familiar with the process of dration known as spray drying In this process, a concentratedsolution of coffee in water is sprayed though a disk with manysmall holes in it The surface area of the original coffeegrounds is increased many times, making dehydration of thedry product much more efficient Freeze-drying is a method ofpreservation that makes use of the physical principle known assublimation Sublimation is the process by which a solidpasses directly to the gaseous phase without first melting.Freeze-drying is a desirable way of preserving food because atlow temperatures (commonly around 14°F to –13°F [–10°C to–25°C]) chemical reactions take place very slowly andpathogens have difficulty surviving The food to be preserved
dehy-by this method is first frozen and then placed into a vacuumchamber Water in the food first freezes and then sublimes,leaving a moisture content in the final product of as low as0.5%
The precise mechanism by which salting preserves food
is not entirely understood It is known that salt binds with watermolecules and thus acts as a dehydrating agent in foods A highlevel of salinity may also impair the conditions under whichpathogens can survive In any case, the value of adding salt tofoods for preservation has been well known for centuries Sugarappears to have effects similar to those of salt in preventingspoilage of food The use of either compound (and of certain
Trang 11Food preservation • WORLD OF MICROBIOLOGY AND IMMUNOLOGY
other natural materials) is known as curing A desirable side
effect of using salt or sugar as a food preservative is, of course,
the pleasant flavor each compound adds to the final product
Curing can be accomplished in a variety of ways Meatscan be submerged in a salt solution known as brine, for exam-
ple, or the salt can be rubbed on the meat by hand The
injec-tion of salt soluinjec-tions into meats has also become popular Food
scientists have now learned that a number of factors relating to
the food product and to the preservative conditions affect the
efficiency of curing Some of the food factors include the type
of food being preserved, the fat content, and the size of treated
pieces Preservative factors include brine temperature and
concentration, and the presence of impurities
Curing is used with certain fruits and vegetables, such
as cabbage (in the making of sauerkraut), cucumbers (in the
making of pickles), and olives It is probably most popular,
however, in the preservation of meats and fish Honey-cured
hams, bacon, and corned beef (“corn” is a term for a form of
salt crystals) are common examples
Freezing is an effective form of food preservationbecause the pathogens that cause food spoilage are killed or do
not grow very rapidly at reduced temperatures The process is
less effective in food preservation than are thermal techniques
such as boiling because pathogens are more likely to be able
to survive cold temperatures than hot temperatures In fact,
one of the problems surrounding the use of freezing as a
method of food preservation is the danger that pathogens
deactivated (but not killed) by the process will once again
become active when the frozen food thaws
A number of factors are involved in the selectionof thebest approach to the freezing of foods, including the tempera-
ture to be used, the rate at which freezing is to take place, and
the actual method used to freeze the food Because of
differ-ences in cellular composition, foods actually begin to freeze at
different temperatures ranging from about 31°F (–0.6°C) for
some kinds of fish to 19°F (–7°C) for some kinds of fruits
The rate at which food is frozen is also a factor, rily because of aesthetic reasons The more slowly food is
prima-frozen, the larger the ice crystals that are formed Large ice
crystals have the tendency to cause rupture of cells and the
destruction of texture in meats, fish, vegetables, and fruits In
order to deal with this problem, the technique of
quick-freez-ing has been developed In quick-freezquick-freez-ing, a food is cooled to
or below its freezing point as quickly as possible The product
thus obtained, when thawed, tends to have a firm, more
natu-ral texture than is the case with most slow-frozen foods
About a half dozen methods for the freezing of foodshave been developed One, described as the plate, or contact,
freezing technique, was invented by the American inventor
Charles Birdseye in 1929 In this method, food to be frozen is
placed on a refrigerated plate and cooled to a temperature less
than its freezing point Alternatively, the food may be placed
between two parallel refrigerated plates and frozen Another
technique for freezing foods is by immersion in very cold
liq-uids At one time, sodium chloride brine solutions were widely
used for this purpose A 10% brine solution, for example, has
a freezing point of about 21°F (–6°C), well within the desired
freezing range for many foods More recently, liquid nitrogen
has been used for immersion freezing The temperature of uid nitrogen is about –320°F (–195.5°C), so that foodsimmersed in this substance freeze very quickly
liq-As with most methods of food preservation, freezingworks better with some foods than with others Fish, meat,poultry, and citrus fruit juices (such as frozen orange juiceconcentrate) are among the foods most commonly preserved
by this method
by which a natural food is converted into another form bypathogens It is a process in which food spoils, but results inthe formation of an edible product Perhaps the best example
of such a food is cheese Fresh milk does not remain in ediblecondition for a very long period of time Its pHis such thatharmful pathogens begin to grow in it very rapidly Earlyhumans discovered, however, that the spoilage of milk can becontrolled in such a way as to produce a new product, cheese.Bread is another food product made by the process offermentation Flour, water, sugar, milk, and other raw materi-als are mixed together with yeasts and then baked The addi-tion of yeasts brings about the fermentation of sugars present
in the mixture, resulting in the formation of a product that willremain edible much longer than will the original raw materi-als used in the bread-making process
Heating food is an effective way of preserving itbecause the great majority of harmful pathogens are killed attemperatures close to the boiling point of water In this respect,heating foods is a form of food preservation comparable tothat of freezing but much superior to it in its effectiveness Apreliminary step in many other forms of food preservation,especially forms that make use of packaging, is to heat thefoods to temperatures sufficiently high to destroy pathogens
In many cases, foods are actually cooked prior to theirbeing packaged and stored In other cases, cooking is neitherappropriate nor necessary The most familiar example of thelatter situation is pasteurization During the 1860s, the Frenchbacteriologist Louis Pasteur discovered that pathogens infoods could be destroyed by heating those foods to a certainminimum temperature The process was particularly appealingfor the preservation of milk since preserving milk by boiling
is not a practical approach Conventional methods of ization called for the heating of milk to a temperature between
pasteur-145 and 149°F (63 and 65°C) for a period of about 30 minutes,and then cooling it to room temperature In a more recent revi-sion of that process, milk can also be “flash-pasteurized” byraising its temperature to about 160°F (71°C) for a minimum
of 15 seconds, with equally successful results A processknown as ultra-high-pasteurization uses even higher tempera-tures, of the order of 194–266°F (90–130°C), for periods of asecond or more
One of the most common methods for preserving foodstoday is to enclose them in a sterile container The term “can-ning” refers to this method although the specific container can
be glass, plastic, or some other material as well as a metal can,from which the procedure originally obtained its name Thebasic principle behind canning is that a food is sterilized, usu-ally by heating, and then placed within an air-tight container
In the absence of air, no new pathogens can gain access to the
Trang 12Food safety
sterilized food In most canning operations, the food to be
packaged is first prepared in some way—cleaned, peeled,
sliced, chopped, or treated in some other way—and then
placed directly into the container The container is then placed
in hot water or some other environment where its temperature
is raised above the boiling point of water for some period of
time This heating process achieves two goals at once First, it
kills the vast majority of pathogens that may be present in the
container Second, it forces out most of the air above the food
in the container
After heating has been completed, the top of the tainer is sealed In home canning procedures, one way of seal-
con-ing the (usually glass) container is to place a layer of melted
paraffin directly on top of the food As the paraffin cools, it
forms a tight solid seal on top of the food Instead of or in
addition to the paraffin seal, the container is also sealed with a
metal screw top containing a rubber gasket The first glass jar
designed for this type of home canning operation, the Mason
jar, was patented in 1858
The commercial packaging of foods frequently makesuse of tin, aluminum, or other kinds of metallic cans The tech-
nology for this kind of canning was first developed in the
mid-1800s, when individual workers hand-sealed cans after foods
had been cooked within them At this stage, a single worker
could seldom produce more than 100 “canisters” (from which
the word “can” later came) of food a day With the development
of far more efficient canning machines in the late nineteenth
century, the mass production of canned foods became a reality
As with home canning, the process of preserving foods
in metal cans is simple in concept The foods are prepared and
the empty cans are sterilized The prepared foods are then
added to the sterile metal can, the filled can is heated to a
ster-ilizing temperature, and the cans are then sealed by a machine
Modern machines are capable of moving a minimum of 1,000
cans per minute through the sealing operation
The majority of food preservation operations usedtoday also employ some kind of chemical additive to reduce
spoilage Of the many dozens of chemical additives available,
all are designed either to kill or retard the growth of
pathogens or to prevent or retard chemical reactions that
result in the oxidation of foods Some familiar examples of
the former class of food additives are sodium benzoate and
benzoic acid; calcium, sodium propionate, and propionic
acid; calcium, potassium, sodium sorbate, and sorbic acid;
and sodium and potassium sulfite Examples of the latter
class of additives include calcium, sodium ascorbate, and
ascorbic acid (vitamin C); butylated hydroxyanisole (BHA)
and butylated hydroxytoluene (BHT); lecithin; and sodium
and potassium sulfite and sulfur dioxide
A special class of additives that reduce oxidation isknown as the sequestrants Sequestrants are compounds that
“capture” metallic ions, such as those of copper, iron, and
nickel, and remove them from contact with foods The
removal of these ions helps preserve foods because in their
free state they increase the rate at which oxidation of foods
takes place Some examples of sequestrants used as food
preservatives are ethylenediamine-tetraacetic acid (EDTA),
citric acid, sorbitol, and tartaric acid
The lethal effects of radiation on pathogens has beenknown for many years Since the 1950s, research in the UnitedStates has been directed at the use of this technique for pre-serving certain kinds of food The radiation used for foodpreservation is normally gamma radiation from radioactiveisotopes or machine-generated x rays or electron beams One
of the first applications of radiation for food preservation was
in the treatment of various kinds of herbs and spices, an cation approved by the U.S Food and Drug Administration(FDA) in 1983 In 1985, the FDA extended its approval to theuse of radiation for the treatment of pork as a means ofdestroying the pathogens that cause trichinosis Experts pre-dict that the ease and efficiency of food preservation by means
appli-of radiation will develop considerably in the future Thatfuture is somewhat clouded, however, by fears expressed bysome scientists and members of the general public about thedangers that irradiated foods may have for humans In addition
to a generalized concern about the possibilities of beingexposed to additional levels of radiation in irradiated foods(not a possibility), critics have raised questions about the cre-ation of new and possibly harmful compounds in food that hasbeen exposed to radiation
See also Biotechnology; Botulism; Food safety; History of
microbiology; History of public health; Salmonella food soning; Winemaking
poi-FOOD SAFETY
Food safety
Food is a source of nutrients not only to humans but to
mois-ture that are often present in foods present an ideal ment for the growth of various microorganisms Themonitoring of the raw food and of any processing stepsrequired prior to the consumption of the food are necessary toprevent transmission of disease-causing microorganisms fromthe food to humans
microorganisms, chemicals, and heavy metals can cause borne maladies These agents are responsible for over 200 dif-ferent foodborne diseases In the United States alone,foodborne diseases cause an estimated 75 million illnessesevery year, and 7,000 to 9,000 deaths
food-Aside from the human toll, the economic consequences
of foodborne illnesses are considerable In 1988, for example,human foodborne diarrheal disease in the United States costthe U.S economy an estimated five to seven billion dollars inmedical care and lost productivity
The threat from foodborne disease causing agents is notequal For example, the Norwalk-like viruses cause approxi-mately 9 million illnesses each year, but the fatality rate is
only 0.001% Vibrio vulnificus causes fewer than 50 cases
each year but almost 40% of those people die Finally, the
bac-teria Salmonella, Lisbac-teria monocytogenes, and Toxoplasma gondii cause only about 20% of the total cases but are respon-
sible for almost 80% of the total deaths from foodborne nesses
Trang 13ill-Food safety • WORLD OF MICROBIOLOGY AND IMMUNOLOGY
that Campylobacter jejuni is the leading cause of foodborne
illness in the United States Another bacteria, Salmonella is
the next leading cause The third cause of foodborne illness is
the bacterium Escherichia coli O157:H7 Poultry and ground
meat are prime targets for bacterial contamination Indeed,
monitoring studies have demonstrated that some 70–90% of
poultry carry Campylobacter jejuni.
Food safety needs to consider the influences of themicrobial pathogen, the human host and the exposure of the
food to the environment that promotes contamination The
environment can include the physical parameters such as the
temperature, moisture, or other such factors As well the
envi-ronment can be the site of the foodstuff, such as the farmyard
or the processing plant Ensuring safety of food from
micro-bial threat must consider all three of the influences For
exam-ple, reducing the length of time that a food is exposed to a
questionable environment, but doing nothing to remove
microbes from the environment only slightly reduces the risk
of food contamination Significant protection of foods
depends on reducing the risk from the environment,
microor-ganism of interest and of the human host
The treatment of foods prior to consumption is a vitalfactor in ensuring food safety Some of these treatments havebeen known for a long time Salting of meats and drying offoods on long sea voyages was practiced several centuriesago, for example The canning of foods began in the eigh-teenth century Within the last 150 years, the link betweenhygienic conditions and the quality and safety of foods wasrecognized Some of the advances in food safety arose fromthe need for foods on long military campaigns, such as thoseundertaken by Napoleon in the nineteenth century Also,advances were spurred by the demands of the nascent foodindustry As the distance between the farm and the marketbegan to grow larger, and the shipping of food became morecommonplace, the problems of food contamination becameevident Practices to render food safe for shipping, storageand subsequent consumption were necessary if the foodindustry was to grow and flourish
The heat treatment of milk known as pasteurization
began in the 1890s Pasteurization is the transient exposure ofmilk to temperatures high enough to kill microbes, while pre-serving the taste and visual quality of the milk Milk is nowroutinely pasteurized before sale to kill any bacteria thatwould otherwise growth in the wonderful growth medium thatthe liquid provides Within the past thirty years the use of radi-ation to kill microbes in food has been utilized While a veryeffective method to ensure food safety, irradiation is still sub-ject to consumer uncertainty, which has to date limited its use-fulness As a final example, within the past two decades, thedanger posed by intestinal bacterial pathogens, particularly
Escherichia coli O157:H7 has resulted in the heightened
recognition of the need for proper food preparation and sonal hygiene
per-Food safety is also dependent on the development andenforcement of standards of food preparation, handling andinspection Often the mandated inspection of foods requiresthe food to be examined in certain ways and to achieve setbenchmarks of quality (such as the total absence of fecal col-iform bacteria) Violation of the quality standards can result inthe immediate shut down of the food processing operationuntil the problem is located and rectified
Most of the food safety legislation and inspectionefforts are aimed at the processing of food It is difficult tomonitor the home environment and to enforce codes ofhygiene there Yet, food safety in the home is of paramountimportance The improper storage of foods prepared with raw
or undercooked eggs, for example, can lead to the growth ofmicroorganisms in the food Depending on the microbe andwhether toxins are produced, food poisoning or food intoxica-tion can result from eating the food dish Additionally,improper cleaning of cutting and other preparation surfacescan lead to the cross-contamination of one food by another.Good hygienic practices are as important in the home as on thefarm, in the feedlot, and in the processing plant
See also BSE and CJD disease; BSE and CJD disease,
advances in research; BSE and CJD disease, ethical issues andsocio-economic impact; Enterotoxin and exotoxin; Foodpreservation; Transmission of pathogens
Raw oysters can harbor microbial toxins.
Trang 14Foot-and-mouth disease
Foot-and-mouth disease
Often inaccurately called hoof-and-mouth disease, this highly
contagious virus causes blisters in the mouth and on the feet
surrounding hoofs of animals with cleft, or divided hoofs, such
as sheep, cattle and hogs The disease was first noted in Europe
in 1809; the first outbreak in the United States came in 1870
Although it seldom spreads to humans, it can be transmitted
through contaminated milk or the handling of infected animals
Outbreaks are expensive for the animal owners whomust kill the infected animals and incinerate or bury or them in
quicklime Then the animals’ living quarters are disinfected,
while feed and litter are burned The farm is quarantined by
state and federal officials who can decide to extend the
quar-antine to the general area or the whole state Friedrich August
Löffler (1852–1915), a German bacteriologist who discovered
the bacillus of diphtheriain 1884, also demonstrated in 1898
that a virus causes hoof-and-mouth disease It was the first time
a virus was reported to be the cause of an animal disease
An infected animal can take up to four days to beginshowing symptoms of fever, smacking of lips and drooling
Eventually, blisters appear on the mouth, tongue and inside of
the lips and the animal becomes lame just before blisters
appear in the hoof area
Löffler, working with Dr Paul Frosch (1860–1928), aveterinary bacteriologist, extracted lymph from the blisters on
the mouths and udders of diseased cattle The lymph wasdiluted in sterile water and passed through filters Theresearchers expected the filtrate to be an antitoxin of foot-and-mouth disease similar to the one for smallpox
But Löffler and Frosch were wrong; when the filtrateswere injected into healthy animals, they became sick.Therefore, they concluded the causative agent was not a bac-terial toxin, but instead was a non-toxin producing bacteriumtoo small to be seen under the microscope, yet small enough
to pass through the filters It wasn’t until 1957 that scientistswere able to get their first look at the causative agent, one ofthe smallest virusesto cause an animal disease
In February, 2001, a devastating outbreak of mouth disease began among the stock of England’s pig, sheep,and cattle ranchers Epidemiologists (investigators in infec-tious disease) determined that the outbreak began in a swill(garbage) feeding farm in one county, and spread first by thewind to a nearby sheep farm, then by sheep markets to farmsacross the English countryside Even before the outbreak wasdetected, the virus had infected livestock in 43 farms Despitemassive quarantining and culling of herds (over 4 million ani-mals were destroyed), by the time the outbreak was containedalmost a year later, the disease had spread to areas of Ireland,France, and the Netherlands
foot-and-English citizens lost billions of dollars worth of income
as markets for English meat and dairy products evaporated,
Destruction of sheep to prevent the spread of infection during an outbreak of foot-and-mouth disease.
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animals were decimated, and tourists avoided the English
countryside Use of an available vaccineto attempt to curb the
epidemic was rejected by most scientists, as the virus
incuba-tion time was short (often less than 72 hours), and the
immu-nitygained from the vaccine was short-lived Meanwhile, the
Unites States and other countries adopted inclusive measures
to prevent the importation of the foot-and-mouth virus, from
carefully restricting the importation of animal products, to the
sanitizing of shoes of airplane passengers arriving in the U.S
from England As of April 2002, the outbreak continued to be
contained, with the last confirmed foot-and-mouth case in
England occurring six months prior at a farm in
Northumberland, and the restoration of
“Foot-and-mouth-Free” status restored to livestock herds of the United Kingdom
by the World Organization for Animal Health (Office
Internationale des Epizooties)
See also Animal models of infection; Epidemics, viral;
Epidemiology, tracking diseases with technology;
Epidemiology; Veterinary microbiology
FORENSIC IDENTIFICATION OF
MICRO-ORGANISMS • see GENETIC IDENTIFICATION OF MICRO
-ORGANISMS
FORENSIC IMMUNOLOGY AND
BACTERI-OLOGY • see GENETIC IDENTIFICATION OF MICRO
-ORGANISMS
FOSSILIZATION OF BACTERIA
Fossilization of bacteria
Studies of fossilization of bacteriaprovide an indication of the
age of ancient bacteria Fossils of cyanobacteria or
“blue-green algae” have been recovered from rocks that are nearly
3.5 million years old Bacteria known as magnetobacteria
form very small crystals of a magnetic compound inside the
cells These crystals have been found inside rock that is two
billion years old
The fossilization process in cyanobacteria and otherbacteria appears to depend on the ability of the bacteria to trap
sediment and metals from the surrounding solution
Cyanobacteria tend to grow as mats in their aquatic
environ-ment The mats can retain sedienviron-ment Over time and under
pres-sure the sediment entraps the bacteria in rock As with other
living organisms, the internal structure of such bacteria is
replaced by minerals, notably pyrite or siderite (iron
carbon-ate) The result, after thousands to millions of years, is a
replica of the once-living cell
Other bacteria that elaborate a carbohydrate networkaround themselves also can become fossilized The evidence
for this type of fossilization rests with laboratory experiments
where bacteria are incubated in a metal-containing solution
under conditions of temperature and pressure that attempt to
mimic the forces found in geological formations Experiments
with Bacillus subtilis demonstrated that the bacteria act as a
site of precipitation for silica, the ferric form of iron, and ofelemental gold The binding of some of the metal ions toavailable sites within the carbohydrate network then acts todrive the precipitation of unstable metals out of solution andonto the previously deposited metal The resulting cascade ofprecipitation can encase the entire bacterium in metallicspecies On primordial Earth, this metal binding may havebeen the beginning of the fossilization process
The deposition of metals inside carbohydrate networkslike the capsule or exopolysaccharide surrounding bacteria is anormal feature of bacterial growth Indeed, metal deposition canchange the three-dimensional arrangement of the carbohydratestrands so as to make the penetration of antibacterial agentsthrough the matrix more difficult In an environment—such asoccurs in the lungs of a cystic fibrosis patient— this micro-fos-silization of bacteria confers a survival advantage to the cells
In contrast to fossils of organisms such as dinosaurs, thepreservation of internal detail of microorganisms seldomoccurs Prokaryotes have little internal structure to preserve.However, the mere presence of the microfossils is valuable, asthey can indicate the presence of microbial life at that point ingeological time
Bacteria have been fossilized in amber, which is silized tree resin Several reports have described the resuscita-tion of bacteria recovered from amber as well as bacteriarecovered from a crystal in rock that is millions of years old.Although these claims have been disputed, a number of micro-biologists assert that the care exercised by the experimenterslends increases the validity of their studies
fos-In the late 1990s a meteorite from the planet Mars wasshown to contain bodies that appeared similar to bacterial fos-sils that have been found in rocks on Earth Since then, furtherstudies have indicated that the bodies may have arisen by inor-ganic (non-living) processes Nonetheless, the possibility thatthese bodies are the first extraterrestrial bacterial fossils hasnot been definitively ruled out
See also Bacterial surface layers; Biogeochemical cycles;
Glycocalyx
FRIEND, CHARLOTTE (1921-1987)
Friend, Charlotte
American microbiologist
As the first scientist to discover a direct link between viruses
and cancer, Charlotte Friend made important breakthroughs incancer research, particularly that of leukemia She was suc-cessful in immunizing mice against leukemia and in pointing
a way toward new methods of treating the disease Because ofFriend’s work, medical researchers developed a greater under-standing of cancer and how it can be fought
Friend was born on March 11, 1921, in New York City toRussian immigrants Her father died of endocarditis (heart
influenced her early decision to enter the medical field; at ageten she wrote a school composition entitled, “Why I Want toBecome a Bacteriologist.” Her mother’s job as a pharmacist
Trang 16Fume hood
also exposed Friend to medicine After graduating from Hunter
College in 1944, she immediately enlisted in the U.S Navy
dur-ing World War II, risdur-ing to the rank of lieutenant junior grade
After the war, Friend entered graduate school at YaleUniversity, obtaining her Ph.D in bacteriology in 1950 Soon
afterward, she was hired by the Memorial Sloan-Kettering
Institute for Cancer Research, and in 1952, became an associate
professor in microbiology at Cornell University, which had just
set up a joint program with the institute During that time,
Friend became interested in cancer, particularly leukemia, a
cancer of blood-forming organs that was a leading killer of
chil-dren Her research on the cause of this disease led her to believe
that, contrary to the prevailing medical opinion, leukemia in
mice is caused by a virus To confirm her theory, Friend took
samples of leukemia tissue from mice and, after putting the
material through a filter to remove cells, injected it into healthy
mice These animals developed leukemia, indicating that the
cause of the disease was a substance smaller than a cell Using
photo-graph the virus she believed responsible for leukemia
However, when Friend presented her findings at the April
1956, annual meeting of the American Association for Cancer
Research, she was denounced by many other researchers, who
refused to believe that a virus was responsible for leukemia
Over the next year support for Friend’s theory mounted, first as
Dr Jacob Furth declared that his experiments had confirmed the
existence of such a virus in mice with leukemia Even more
importantly, Friend was successful in vaccinating mice against
leukemia by injecting a weakened form of the virus (now called
the “Friend virus”) into healthy mice, so they could develop
antibodies to fight off the normal virus Friend’s presentation of
a paper on this vaccineat the cancer research association’s 1957
meeting succeeded in laying to rest the skepticism that had
greeted her the previous year
In 1962, Friend was honored with the Alfred P SloanAward for Cancer Research and another award from the
American Cancer Society for her work The next year she
became a member of the New York Academy of Sciences, an
organization that has members from all fifty states and more
than eighty countries In 1966, Friend left Sloan-Kettering to
become a professor and director at the Center for
Experimental Cell Biology at the newly formed medical
school of New York’s Mount Sinai Hospital During this time,
she continued her research on leukemia, and in 1972, she
announced the discovery of a method of altering a leukemia
mouse cell in a test tube so that it would no longer multiply
Through chemical treatment, the malignant red blood cell
could be made to produce hemoglobin, as do normal cells
Although the virus responsible for leukemia in mice hasbeen discovered, there is no confirmation that a virus causes
leukemia in humans Likewise, her treatment for malignant
red blood cells has limited application, because it will not
work outside of test tubes Nonetheless, Friend had pointed
out a possible cause of cancer and developed a first step
toward fighting leukemia (and possibly other cancers) by
tar-geting specific cells
In 1976, Friend was elected president of the AmericanAssociation for Cancer Research, the same organization
whose members had so strongly criticized her twenty yearsearlier Two years later, she was chosen the first woman pres-ident of the New York Academy of Sciences Friend was longactive in supporting other women scientists and in speakingout on women’s issues During her later years, she expressedconcern over the tendency to emphasize patient care overbasic research, feeling that without sufficient funding forresearch, new breakthroughs in patient care would be impos-sible Friend died on January 13, 1987, of lymphoma
See also Viral vectors in gene therapy; Virology; Virus
repli-cation; Viruses and responses to viral infection
FUME HOOD
Fume hood
A fume hood is an enclosed work space in a laboratory that vents the outward flow of air Fume hoods cab be designed forwork with inorganic or radioactive materials, or with biologicalmaterials Biological fume hoods can be equipped with filters,
pre-to ensure that the air entering and exiting the cabinet is sterile.This minimizes the risk of exposure of laboratory personnel tobiological agents that could be a health threat Also, the worksurfaces and materials inside the fume hood are protected from
Charlotte Friend, an important cancer researcher.
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particular relevance in some viral research, where the tissue
sur-faces used to grow the virus are prone to contamination
The design of fume hoods differs, depending on theintended purpose (general purpose, chemical, radioisotope,
biological) But all fume hoods share the feature of an
inward flow of air In biological fume hoods the flow of
ster-ile air is typically from the back of the cabinet toward the
laboratory worker, and from the top of the fume hood
down-ward across the opening at the front of the hood This pattern
of airflow ensures that any microorganismsresiding on the
laboratory worker are not carried into the work surface, and
that no air from inside the cabinet escapes to the outside of
the cabinet Any air that is exhausted back into the laboratory
first passes through filters that are designed to remove
logical and viral contaminants The most popular type of
bio-logical filter is the high-energy particulate air (or HEPA)
filter
Biological fume hoods can have a moveable, protectiveglass partition at the front Most hoods also have a gas source
inside, so that sterile work, such as the flaming of inoculation
loops, can be done The fume hood should be positioned in an
area of the laboratory where there is less traffic back and forth,
which lessens the turbulence of air outside the fume hood
The filtering system of biological fume hoods restrictsits use to biological work Work involving noxious chemicals
and vapors needs to be conducted in another, specially
designed chemical fume hood
The construction of fume hoods is conducted according
to strict protocols of safety and performance monitoring In
normal laboratory use, the continued performance of a fume
hood is regularly monitored and test results recorded Often
such checks are a mandatory requirement of the ongoing
cer-tification of an analysis laboratory Accordingly, laboratories
must properly maintain and use fume hoods to continue to
meet operating rules and regulations
See also Bioterrorism, protective measures; Containment and
release prevention protocol
FUNGAL GENETICS
Fungal genetics
large, fleshy, and often colorful mushrooms or toadstools,
fil-amentous organisms only just visible to the naked eye, and
single-celled organisms such as yeasts Molds are important
agents of decay They also produce a large number of
indus-trially important compounds like antibiotics(penicillin,
grise-ofulvin, etc.), organic acids (citric acid, gluconic acid, etc.),
(soft-ening and flavoring of cheese, shoyu soy sauce, etc.), and a
number of other miscellaneous products (gibberellins, ergot
alkaloids, steroid bioconversions) As late as 1974 the only
widely applicable techniques for strain improvement were
mutation, screening, and selection While these techniques
proved dramatically successful in improving penicillin
pro-duction, they deflected attempts to employ a more
sophisti-cated approach to genetic manipulation The study of fungalgenetics has recently changed beyond all recognition.The natural genetic variation present in fungal specieshas been characterized using molecular methods such as elec-trophoretic karyotyping, restriction fragment length polymor-phism, DNAfinger printing, and DNA sequence comparisons.The causes for the variation include chromosomal polymor-phism, changes in repetitive DNA, transposons, virus-likeelements, and mitochondrial plasmids
Genetic recombination occurs naturally in many fungi
Many industrially important fungi such as Aspergilli and Penicillia lack sexuality, so in these species parasexual systems
(cycles) provide the basis for genetic study and breeding grams The parasexual cycle is a series of events that can beinduced when two genetically different strains are growntogether in the laboratory A heterokaryon, which is mycelium
pro-with two different nuclei derived from two different haploidstrains, is produced by the fusion of hyphae Increased peni-cillin titer in the haploid progeny of parasexual crosses has been
achieved in Penicillium chrysogenum A more direct approach
has been developed using protoplasts These are isolated fromvegetative cells of fungi or yeasts by removing the cell wall bydigestion using a cell wall degrading enzyme Protoplasts fromthe two strains can be fused by treatment with polyethylene gly-col Protoplast fusion in fungi initiates the parasexual cycle,resulting in the formation of diploidy and mitotic recombinationand segregation A selection procedure to screen such fusants isdone using genetic markers A good example of applying thistechnique is the fusion of a fast growing but poor glucoamylaseproducer with a slow growing but excellent producer of glu-coamylase The desired result will be a strain that is both fastgrowing and an excellent producer of enzyme
The realization that transformation of genetic materialinto fungi can occur came with the discovery that yeasts like
Saccharomyces cerevisiae and filamentous fungi like
Podospora anserine contain plasmids Currently
transforma-tion technology is largely based on the use of Neurospora crassa and Aspergillus nidulans, though methods for use in
filamentous organisms are being developed The protocolsused in transformation of filamentous fungi involve cloning
the desired gene into the plasmid from E coli or a plasmid
constructed from genetic material from E coli and Saccharomyces cerevisiae Protoplasts from the recipient
strains are then formed and mixed with the plasmid Afterincubating for a short time to allow for the uptake of the plas-mid DNA, the protoplasts are allowed to regenerate and thecells are screened for the presence of the specific marker.The application of recombinant DNA to yeasts and fila-mentous fungi has opened up new possibilities in relation tothe construction of highly productive strains The filamentousfungi are now established as potent host organisms for the pro-duction of heterologous proteins This is particularly useful asexpression of specific proteins can reach relatively high levels
Using Aspergillus as a host for reproduction has led to the
pro-duction of many recombinant products like human therapeuticproteins, including growth factors, cytokines, and hormones
While expression can be good in E coli, lack of
posttransla-tional modifications has limited their usage The use of
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production of extracellular proteins Most of the initial
advances for the production of heterologous proteins has been
with filamentous fungi, namely Aspergillus nidulans.
Although this organism is not of industrial importance it is
nevertheless genetically well characterized; in addition, this
organism has secretion signals that result in recombinant
pro-teins being identical to mammalian cells This allows the
prod-uct from such systems to be used safely in human therapy
Other systems that have been used include Pichia and
Trichoderma, which have been widely used in industry Now
that the complete genome of S cerevisiae has been
deci-phered, and with more fungi genomes in the pipeline, an even
better understanding of fungal genetics is certain
See also Cell cycle (Eukaryotic), genetic regulation of;
Microbial genetics
FUNGI
Fungi
Fungi play an essential role in breaking down organic matter
and thereby allowing nutrients to be recycled in nature As
such, they are important decomposers and without them living
communities would become buried in their own waste Somefungi, the saprobes, get their nutrients from nonliving organicmatter, such as dead plants and animal wastes, clothing, paper,leather, and other materials Others, the parasites, get nutri-ents from the tissues of living organisms Both types of fungiobtain nutrients by secreting enzymes from their cells thatbreak down large organic molecules into smaller components.The fungi cells can then absorb the nutrients
Although the term fungus invokes unpleasant imagesfor some people, fungi are a source of antibiotics, vitamins,and industrial chemicals Yeast, a kind of fungi, is used to fer-ment bread and alcoholic beverages Nevertheless, fungi alsocause athlete’s foot, yeast infections, food spoilage, wheatand corn diseases, and, perhaps most well known, the Irishpotato famine of 1843–1847 (caused by the fungus
Phytophthora infestans), which contributed to the deaths of
250,000 people in Ireland
Fungi are not plants, and are unique and separate forms
of life that are classified in their own kingdom Approximately75,000 species of fungi have been described, and scientistsestimate that more than 90% of all fungi species on the planethave yet to be discovered The fungi body, called mycelium, iscomposed of threadlike filaments called hyphae All fungi can
Fungus colony.