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NAME: WASWA WALTER WAKHUNGU
UNIVERSITY: PWANI UNIVERSITY
ADM.NO. : SG26/PU/36067/16
COURSE: MASTERS OF SCIENCE [MICROBIOLOGY]
DEPARTMENT: BIOLOGICAL SCIENCE
SCHOOL: SCHOOL OF PURE AND APPLIED
UNIT: ADVANCED MYCOLOGY
UNIT CODE: SBT G805
LECTURER: DR. JOYCE JEFWA
ASSIGNMENT: Economic and practical food and beverage, Health applications of mycology
A. Food sources
B. Fermenters
C. Wine And Beer Making
D. Leavening Agent
E. Natural Food Flavor And Color
F. Drugs
G. Human Disease
Date : 24/11/2016
A. FOOD
1. Protein source
A large range of edible fungi are cultured. Agaricius bisporus is cultivated widely in western
countries. In addition, Shii-take (Lentinus edodes), Straw mushroom (Flammulina velutipes),
Oyster mushroom (Pleurotus ostreatus), and Chinese Black mushroom (Auricularia polytricha)
are cultured in various Asian countries, and increasingly in western countries. The truffle
industry is economically important in southern Europe and production is expanding in the
southern hemisphere. Finally, edible mushrooms are picked from the wild, especially in Europe.
Many of the fungi are eaten fresh, but there is also a market for dried mushrooms and canned
truffles.
Fungi are ideal food becoming an ideal source of myco-protein , healthy alternative to meat.
They have a fairly high content of protein (typically 20-30% dry matter as crude protein) which
contains all of the essential amino acids. Fungal biomass is also a source of dietary fibre, and is
virtually free of cholesterol. Mushrooms are cultivated around the world, global annual
production being in the region of 8 million metric tones eg Agaricus spp, the mycelium of a
species of Fusarium.
The morel is not commonly seen in shops. The ascocarp is hollow and delicate. The structure is
pointed and rarely higher than 10cm. © Dave Powell , USDA Forest Service. Image 0808042.
http://www.ipmimages.org.
Pleurotus ostreatus, also known as Oyster mushroom. © Robert L. Anderson, USDA Forest
Service. Image 0590031. http://www.ipmimages.org.
Fruiting body of Auricularia. This fungus is found on the dying branches of trees throughout the
University grounds.
B. FERMENTER
1. Soy Sauce
We tend to take a variety of foods and food additives for granted, without being aware of the
processes which get them to the table. One such food is Soy Sauce and its partner bean curd.
Soy sauce (shoyu) is a dark brown, salty liquid, high in amino acids and with a meat-like flavour.
It was first produced in Japan (a similar product is made in other east Asian countries), where
some microbial cultures were used to ferment the unpalatable soy beans. The current industrial
process is highly controlled, used around the world and is based on this original process.
Fermentation is in two stages. Initially, soy beans are soaked, cooked to remove contaminants,
and then mixed with roasted wheat. The fungus Aspergillus oryzae is added to the mix, and the
amended mix kept aerobically for 20 to 40 hours at 25 C. The fungus produces invertases,
amylases and cellulases, which degrade the soy paste. The paste is then mixed and taken into the
second phase of fermentation.
In deep vats, brine is added to the paste and the yeast Saccharomyces rouxii and lactobacilli are
added. Anaerobic conditions develop quickly, preventing further growth of A. oryzae. After
about a month, a sour liquid is apparent. The liquid contains large concentrations of amino acids,
simple sugars and a range of vitamins. After separation and further storage, the liquid is
sterilised, bottled and sold as Soy Sauce. Similar products are called Koji, Idli, Patu, Laochao or
Ogi.
2. Cheese
Production of cheese relies on diverse microbes. The cheese environment is dynamic and the
specific biological interactions complex. Fungi play a role in ripening in two different ways: they
may assist ripening from the outside of the cheese, and they can impart flavours from inside the
cheese.
Various yeast and filamentous fungi colonise the surface of cheeses. The may be surface
contaminants or deliberately inoculated. Their impact will rely on the temperature, water content,
pH, salinity and redox of the substrate.
Soft-ripened cheeses are ripened from the outside in. Penicillium camemberti (=P candidum) is
inoculated onto the surface of cheeses, typically Brie, Camembert and Neufchatel, where growth
over 7 to 70 days imparts a flexible powdery white crust and contributes to the runny texture and
intense flavours of the contents.
Various cheeses are sold that have been stab-inoculated with a strain of Penicillium roquefortii.
The result is a blue streak or vein through the cheese. The fungus imparts a strong, pungent
flavour due to the aerobic production of methyl ketones. Famous blue cheeses include:
Roquefort, Gorgonzola, Stilton, and Danish Blue. The fungus is a widespread spoilage organism
found in cool conditions. It can grow at low oxygen availability and tolerates acidic conditions.
Thus the presence of blue cheeses in your fridge may lead to widespread contamination of
products like bread that use acids as preservatives.
Cheese is susceptible to the growth of fungi. While a huge diversity are associated with
unwanted contamination, some such as Geotrichum candidum have been expoited because they
are thought to impart desirable flavours and assist with the ripening process.
Wine and BeerMaking
Although there is a distinction between beer, wine and liquor as well as other lesser known
alcoholic beverages, they share one thing in common. They are the fermentation products of
yeasts, mostly Saccharomyces cerevisiae or in the case of beers, usually S. carlsburgiensis.
Yeasts, as you recall, are not mycelial. They are unicellular fungi that reproduce asexually by
budding or fission. The reaction by which alcoholic beverages are produced is generally referred
to as fermentation and may be summarized as:
Yeast + Glucose è Alcohol (Ethanol) + CO2
This reaction is also important in baking bread, but the desired product is then the carbon dioxide
rather than alcohol. The production of alcohol occurs best in the absence of oxygen. However,
from the yeast's point of view, alcohol and carbon dioxide are waste products, and as the yeast
continues to grow and metabolize in the sugar solution, the accumulation of alcohol will become
toxic when it reaches a concentration between 14-18%, thereby killing the yeast cells. This is the
reason why the percentage of alcohol in wine and beer can only be approximately 16%. In order
to produce beverages (liquor) with higher concentrations of alcohol, the fermented products must
be distilled. With the genetic manipulation of yeasts, numerous varietal strains have been bred.
This, along with modifications in the brewing process have led to different types of beers. Those
most often seen in North America include:
 Lager. Beers made with yeast that settle on the bottom (Saccharomyces carlsbergensis)
of the container used. Thus, all the yeast and other material settles on the bottom which
results in a clear beer. Most American beers are lagers.
o Pilsner. A colorless lager beer originally brewed in the city of Pilsen. Water used
for this style of beer tend to be harder, with a higher calcium and magnesium
content than water used for lager. The color of pilsner is also lighter than that of
lager beer.
 Ale. Beers made with yeast that floats (Saccharomyces cerevisiae) to the top of the
brewing vats, resulting in a cloudier beer. They tend to have a higher alcohol content than
lagers.
o Stout. A very dark, almost black ale. The dark color and roasted flavor is derived
from the roasted
barley, and/or roasted malt. Beer historians consider it to be the descendant of the
Porter ale.
o Porter. A very dark ale. The darker color and special flavor comes from toasting
the malt before brewing. This usually results in a stronger taste and higher alcohol
content. Considered by beer historians to have evolved into the Stout ale.
C. LEAVENING AGENT
Baker's yeast is the common name for the strains of yeast commonly used as a leavening agent in
baking bread and bakery products, where it converts the fermentable sugars present in the dough
into carbon dioxide and ethanol. Baker's yeast is of the species Saccharomyces cerevisiae
D. FOOD ODOR AND FLAVOR AND FLAVOR
Fungus is primarily responsible for the production of some characteristic odour, flavour, or
texture and may or may not become part of the final edible product. Growing filamentous fungi
on water-soakedseeds of plants is the basis for production of several human food products in
Asia, including soy sauce and various other fermented foods. In soy sauce production soybeans
are soaked, cooked, mashed and fermented with Aspergillus oryzae and A. sojae. Depending on
the size of the factory, the soybeans may be fermented in fist-sized balls (the traditional method)
or on trays. When the substrate has become overgrown with the fungus the material is mixed
with salt and water and the fermentation is completed in the brine. The biggest industrial units
today use a continuous process in which defatted soybean flakes, moistened and autoclaved are
mixed with ground, roasted wheat. The mixture is turned mechanically to ensure even growth of
Aspergillus oryzae and A.sojae for two to three days; then it is transferred to brine and
inoculated with Pediococcus halophilus and 30 days later with Saccharomyces rouxii. The brine
fermentation takes six to nine months to complete, after which the soy sauce is pressure-filtered,
pasteurised and bottled.
While many flavours are produced by bacteria, fungi are responsible for a range of flavours
including terpenes, menthol and lactones. Fungi also produce compounds that deodorise
offensive and neutralise bitter flavours. At present, flavour enhancement is an unimportant area
of the industrial use of fungi.
Colours
Fungi produce a range of compounds that alter the colour of food. For instance, Monoascus
purpureus has been traditionally used for the production of red wine. The pigments are
polyketides that are insoluble in acid conditions. Beta carotene is produced by a range of
Mucorales. This can be added to a variety of foods. Concern with the potentially toxic or allergic
characteristics of some artificial colours has led to a closer examination of colours from natural
sources.
E. DRUGS
Fungi make an extraordinarily important contribution to managing disease in humans and other
animals. At the beginning of the 21st century, Fungi were involved in the industrial processing of
more than 10 of the 20 most profitable products used in human medicine. Two anti-cholesterol
statins, the antibiotic penicillin and the immunosuppressant cyclosporin A are among the top 10.
Each of these has a turn over in excess of $1 billion annually. Drug discovery continues. The
following have recently been approved for human use: Micafungin is an antifungal agent;
mycophenolate is used to prevent tissue rejection; rosuvastatin is usd to reduce cholesterol; and
cefditoren as an antibiotic Antibiotics From Fungi
In 1941, penicillin from the fungus Penicillium chrysogenum was first used successfully to treat
an infection caused by a bacterium. Use of penicilin revolutionised the treatment of pathogenic
disease. Many formally fatal diseases caused by bacteria became treatable, and new forms of
medical intervention were possible.
When penicillin was first produced, the concentration of active ingredient was approximately 1
microgram per ml of broth solution. Today, improved strains and highly developed fermentation
technologies produce more than 700 micrograms per ml of active ingredient.
In the early broths, several closely related molecules were present. These molecules are beta
lactam rings fused to five-membered thiazolidine rings, with a side chain. The side chain can be
chemically modified to provide slightly different properties to the compound.
The natural penicillins have a number of disadvantages. They are destroyed in the acid stomach,
and so cannot be used orally. They are sensitive to beta lactamases, which are produced by
resistant bacteria, thus reducing their effectiveness. Also, they only act on gram positive bacteria.
Modifications to manufacturing conditions have resulted in the development of oral forms.
However, antibiotic resistance among bacteria is becoming an extremely important aspect
determining the long-term use of all antibiotics.
Cephalosporins also contain the beta lactam ring. The original fungus found to produce the
compounds was a Cephalosporium, hence the name. As with penicillin, the cephalosporin
antibiotics have a number of disadvantages. Industrial modification of the active ingredients has
reduced these problems.
The only broadly useful antifungal agent from fungi is griseofulvin. The original source was
Penicillium griseofulvin. Griseofulvin is fungistatic, rather than fungicidal. It is used for the
treatment of dermatophytes, as it accumulates in the hair and skin following topical application.
More recently, several new groups have been developed. Strobilurins target the ubihydroquinone
oxidation centre, and in mammals, the compound from fungi is immediately excreted.
Basidiomycetes, especially from tropical regions, produce an enormous diversity of these
compounds.
Sordarins are structurally complex molecules that show a remarkably narrow range of action
against yeasts and yeast-like fungi. The compounds inhibit protein biosynthesis and so may
become important agents against a number of fungal pathogens of humans.
Echinocandins are cyclic peptides with a long fatty acid side chain. They target cell wall
formation. Semi-synthetic members of the group of compounds include pneumocandins which
are in use in humans.
Immune Suppressants
Cyclosporin A is a primary metabolite of several fungi, including Trichoderma polysporum and
Cylindrocarpon lucidum. Cyclosporin A has proven to be a powerful immunosuppressant in
mammals, being widely used during and after bone marrow and organ transplants in humans.
Cyclosporin A is a cyclic peptide consisting of 11 mainly hydrophobic amino acids. Its inhibition
of lymphocytes was first discovered during the 1970s. Subsequently, the mode of action was
elucidated.
Cyclosporin A binds to a cytosolic protein called cyclophilin. Cyclophilin is found amongst
many different organisms and its form appears highly conserved. Cyclophilin is involved with
folding the protein ribonuclease. However, the Cyclosporin A/cyclophilin complex also binds to
calcineurin. Calcineurin dephosphorylates a transcription factor, thereby triggering transcription
of numerous genes associated with T cell proliferation. When the complex binds to calcineurin,
T cell proliferation is suppressed. The inhibition of T cells proliferation results in the suppression
of the activation process associated with invasion by foreign bodies. As a consequence,
transplant tissues, which are foreign bodies, are not rejected.
Calcineurin is also highly conserved amongst phylogenetically diverse organisms. In fungi such
as the human pathogen Cryptococcus neoformans, calcineurin is necessary for recovery from cell
cycle arrest, growth in hypertonic solutions and regulation of the calcium pump. Thus the
interaction of the Cyclosporin A/cyclophilin complex with calcineurin in Cryptococcus will
result in death of the pathogen. However, in humans, cyclosporin also suppresses the immune
system. The side effect is an unacceptable risk, and Cyclosporin A is not used as a fungicide in
humans at present.
Gliotoxins also have immunological and antibiotic activity. Produced by many fungi including
Aspergillus fumigatus, gliotoxins belong to a class of compounds called
epipolythiodioxopiperazines. The antibiotic activity is widely recognised and considered
uninteresting. However, its effect on the immune system, especially macrophages, is being re-
examined.
A wide range of other compounds with antibiotic activity are also known. They have been
rejected for use in medicine because of unwanted side effects, or instability of the active
compound.
Ergot Alkaloids
Claviceps purpurea is the causal agent of St Anthonies fire, a scourge of the middle ages when
ergots contaminated flour. The ergots contain many alkaloids. Their effects are quite variable.
They act on the sympathetic nervous system resulting in the inhibition of noradrenaline and
sclerotin, causing dilation of blood vessels. They also act directly on the smooth muscles of the
uterus causing contractions, thus their early use to induce abortion. Their strongest effect is
intoxication, caused by lysergic acid amides, one of which is the recreational (and illegal) drug,
LSD.
Seeds of Paspalum replaced by C. paspalli.
Ergot alkaloids have a number of medicinal uses. Perhaps the most widespread use is in the
treatment of migraines. The vasodilator activity reduces tension during an attack. The drugs also
reduce blood pressure, though with untoward side effects. Alkaloids are now produced in culture
by strains of C. fusiformis and C. paspalii.
Statins
Aspergillus terreus, a soil-borne fungus, produces a secondary metabolite called lovastatin and
Phoma sp produces squalestatin. Statins have been used to reduce or remove low density
lipoproteins from blood vessels in humans. In fact, the compounds all act via an enzyme in the
liver that makes cholesterol, lovastatin inhibits HMG CoA reductase and squalestatin inhibits
squalene synthase. By blocking the enzyme, the body removes cholesterol complexes from the
inside of blood vessels. This has the effect of reducing or removing blockages in arteries, and
thereby reducing the chance of a heart attack, strokes and diabetes.
In addition, statins have been implicated in attracting stem cells to damaged tissues. The stem
cells then appear to regenerate the tissue.
Some statins induce problems. One form of the drug has been associated with muscle wastage.
Others appear to lack side effects and have been recommended for wide spread use to control
heart disease.
F. FUNGAL DISEASES IN HUMANS
According to CDC fungi are everywhere. There are approximately 1.5 million different species
of fungi on Earth, but only about 300 of those are known to make people sick.
Fungal diseases are often caused by fungi that are common in the environment. Fungi live
outdoors in soil and on plants and trees as well as on many indoor surfaces and on human skin.
Most fungi are not dangerous, but some types can be harmful to health.In discussing fungal
diseases, the most convenient way of classifying them is to categorize them according to the type
of infection that has occurred: 1. Superficial infections, are caused by fungi that attack the skin
or its appendages (nail, feathers and hair). Some examples of these infection include ringworms,
jock-itch and athlete's foot. These fungi are known as dermatophytes. 2. Systemic infections,
diseases that occur deep within the tissues, involving vital organs and/or the nervous system, and
which may be fatal, but may also be chronic. Entry into the body is usually through inhalation of
spores or open wounds. Blood circulation or respiratory system may then transmit fungus
throughout body and additional infection of internal organ may occur. These fungi, are usually
saprotrophic fungi, growing in the soil. A third, Intermediate infection, is sometimes also
recognize and is intermediate between the two just discussed. The infection will occur below the
skin, but will remain localized
Superficial Infections
The superficial mycoses are the most well known since they can be readily observed. They
commonly occur on the hair, nails and skin of infected individuals. They have been recorded in
various compilations of medical literature for well over a thousand years as ring worm, athlete's
foot, jock itch and piedra. For each type of infection, there can also be a variety of species that
may be causing the disease. Thus, we will only have a general discussion on this group of
diseases.
Ringworm and RelatedDermatophytes
Ringworm usually occurs on the exposed parts of the body, forming circular growths that may
appear darker or lighter than the normal skin color, with symptoms that include skin lesion, rash
and itching of the infected area. Ringworm infections are common where conditions are
unsanitary and crowded with people and has been known since early historical time. There are
indications that ringworm was more prevalent in the recent past than now because of
improvements in sanitary conditions and health habits. The Greeks called it Herpes (=circular or
ring form) and the Romans associated the disease with the larval stage of Tinea, the genus for
clothes moth. The two names were eventually combined to "ringworm". Although the actual
cause of ringworm was not known until the early 1800s, the practice of segregating infected
individuals to prevent spread of the disease indicated that there was knowledge that this disease
was contagious and prevalent, and could be passed from person to person was known prior to the
cause of infection.
It was Gruby that isolated and described one of the ringworm fungi, Trichophyton, meaning
"thread plant", and through inoculation on healthy parts of the scalp, was able to reproduce the
disease. He also carried out the same experiment with several other human pathogenic fungi and
inoculated himself with the pathogen, as well as others. Although this was a great
accomplishment, Gruby also had a great deal of luck since, at the time, isolation of specific fungi
was not common practice, and this was also 30 years prior to the development of techniques to
grow fungi and bacteria in pure culture.
According to Ainsworth, more than 350 species of dermatophytes have been proposed and given
approximately 1,000 names, which has caused some confusion in medical mycology. The
proliferation in names have come about because different researchers have worked with the same
species of a pathogen, in a different place and time, and each were familiar with that particular
isolate of that particular species of fungus and probably not too familiar with that isolate. They
grew it in culture briefly and published on it. Thus, each newly isolated dermatophytic fungus
was given a name, sometimes according to the symptoms with which it was associated or
according to the part of the body affected, i.e. top of the head, neck, face, hand, arm, leg and
foot, or even the geographical region, or sometimes just for the sake of publication (due to the
competitiveness of medical schools) . This led to a great deal of confusion in the understanding
of mycoses.
Although the first species were described in the 1840s, they were little studied until the 1940s,
when the United States military personnel, while fighting in the South Pacific, during WWII,
contracted ringworm and other fungi in the humid tropics (an example of advancement of
knowledge due to driven research). This led to an intensive study, by the government of such
fungi with many species being reduced to synonyms. For example, 172 species were reduced to
Candida albicans.
Epidemiology of Ringworm
Fungi that cause ringworm are widespread, geographically, and usually not of major concern,
other than as cosmetic problems. However, cases in which these diseases cause extreme
disfigurements and infections are known to occur, but are rare outside of the tropics, and are
believed to be due to poor diet and unsanitary condition (Christensen, 1965). At one time
ringworm was a common disease, particularly of children of poorer classes. The inferences
usually is that this was mainly a matter of such children being exposed to less soap and water
than were children of the well-to-do. It is probable that deficiency in diet may also have made
them more susceptible. There have been epidemics of ringworm that have developed in many
cities in the United States. Several species of fungi that cause ringworm are common on adults,
and it seems highly probable that some of them are regularly present without causing any
obvious symptoms. Species that cause ringworm belong to the genera Trichophyton and
Microsporum. These genera of fungi are somewhat unusual in that they produce asexual spores,
but not sexual spores or at least produce them so infrequently that they have not been observed.
Species of fungi causing ringworm can be ecologically divided into three groups:
1. Zoophilic or "animal loving." Species infect animals primarily, e.g. cats, dogs, horses,
cows, poultry, but can readily be transmitted to people. This is probably the most
common source of ringworm in people, and is usually caused by Microsporum canis, a
species usually found on cats and dogs. Animals that are carriers of ringworm do not
necessarily show outward signs of the disease. Symptomless animals and probably people
as well are carriers of these diseases. The infections are spread mainly by spores, but
mycelial fragment in skin and hair can presumably also occur. Spores are very long lived
and can remain alive for years in blankets, in clothing, bedding, combs and other
grooming tools.
2. Anthropophilic or "man loving." Species infect people and cannot be transferred to
animals.
3. Geophilic or "earth loving." Species occur naturally in soil, presumably as a saprobe, but
is capable of infecting animals and people. Another words these are facultative parasites!
There must be great differences among individuals in susceptibility to infection of these
ringworm fungi as well as great differences in susceptibility of an individuals at different times.
There are many questions that remain unanswered concerning this species causing the various
forms of ringworm.
Ringworm infections are conveniently divided into categories, based on the part of the body that
was infected:
 Tinea capitis: Ringworm of the scalp, eyebrow and lashes.
 Tinea corporis: Ringworm of the body.
 Tinea cruris: Ringworm of the groin, perineum and perianal region. Infections are
commonly referred to as "jock itch".
 Tinea unguium: Ringworm of the nail.
 Tinea barbae: Ringworm of the beard.
 Tinea pedis: Ringworm of the feet. Infections are commonly referred to as athlete's
foot.
 Tinea manuum: Ringworm of the hand.
Left Image: Example of Tinea capitis. Middle Image: Example of Tinea corporis. Right Image:
Example of Tinea pedis (Athlete's Foot). All images courtesy of Dr. Glenn Bulmer, from
http://www.medicalmycology.net.
Note that the various "Tinea" names given to the various forms of ringworms do not constitute
species names. A summary of the above ringworm diseases, based on anatomical locations can
be found on the Medline Plus Health Information. There is also discussion on treatment for the
various types of ringworms that have been omitted on this web page. Warning, this site has
very explicit graphics of these diseases!
Presumably infection is spread mainly by air-borne spores which is why veterinarians do not
want ring-worm infected animals to remain in their clinics or hospitals. If this is the case, all of
us at one time must be exposed to infections by various ringworm fungi. Why is it then that few
of us become infected? Why is infection usually localized, e.g. ringworm of the scalp only
occurs in part while most areas are not affected? Surely, there are enough spores produced that
the entire scalp will be infected. Sometimes one person in a family, or animal in a herd, will get
ringworm and it will not spread to others, whereas other times it is highly contagious. There is a
great deal to be learned about ringworm.
An interesting disease that is not one of the ringworms is piedra. This is a disease of the hair
where mycelium grows along the shaft of the hair and often fuses clumps of hair together.
Usually occurs in unsanitary conditions, in tropical countries. To treat piedra the infected hair is
cut or shaved and a topical azole cream, salycylic acid or 2% formaldehyde is applied to the
affected area.
Systemic or Deep-SeatedMycoses
There are a dozen or more species of fungi causing various systemic or deep-seated mycoses in
man and animals. We will discuss several of the more prevalent species or because of some
interesting aspect of the fungus or disease.
Coccidioides immitis, the cause of Coccidioidomycosis (Valley Fever)
This species is endemic to the southwest, in the United States (California, eastward through
Arizona, New Mexico, and western half of Texas), Northern Mexico and some areas of Central
and South America. In the United States, it is most commonly recorded from Kern County, in the
San Joaquin Valley of California. Infection may occur following travel to one of the endemic
areas. The first case of coccidioidomycosis was described in Argentina shortly before 1890; the
patient suffered for seven years before finally dying and by 1915, there were 40 known cases of
this disease, which was thought to be a rare and universally fatal. However, by this time it was
already known that there was a disease called Valley Fever, which was not associated, at that
time, with C. immitis. It would not be until Dickson (1937) that it was realized that Valley Fever
was just a milder form of coccidioidomycosis. Dickson & Gifford (1938) carrying out
ccoocccciiddiiooiiddiinn skin test of long time residents of Kern County demonstrated that 50-70% have, at
some time been infected by this fungus. The test is like a tuberculosis (TB) test where substances
called antigens that are associated with the disease are injected just below the skin, of your
forearm, and the results read 24 to 48 hours later. If an infection of C. immitis has occurred,
antibodies will be produced by the body that will react with the antigen that has been injected,
causing a large red swelling in the area of the injection.
Coccidioides immitis is contracted by inhalation of spores and primarily causes a respiratory
disease in animals and people, but from the lungs it may spread throughout the body by way of
the bloodstream and cause pathologic changes - skin lesions of one sort or another - in just about
all tissues in all parts of the body. In the usual course of events, infection results in a more or less
acute but benign and self-limiting respiratory disease, but once the patient recovers from this,
they are likely to be permanently immune from further infection. Fiese (1958), an authority on
this disease, says that about 60% of those infected have few or no symptoms, and 40% have
symptoms of varying degrees of severity; chills, fever, chest pains, coughing, lassitude -
symptoms typical of a dozen other infections as well. These symptoms develop ten to fourteen
days after infection, and may persist for some time, but eventually, in most cases, the
immunological processes of the body take over and rids it of infection, although lesions and scars
in the lungs may remain. In a relatively few cases (1 in 500) the fungus is disseminated from the
lungs to other parts of the body, and this secondary stage may result in severe lesions in the skin,
bones, and internal organs and the victim will have massive external and internal lesions and
abscesses. If this stage is reached, it is unlikely that the victim will recover, death will occur
within weeks or after a long and lingering illness. Sometime the disease proceeds to a fairly
advanced stage and then remains static for years, and it may regress and later reappear.
Amphotericin B is the drug of choice to treat this disease.
Left Image: Positive reaction to coccidioidin skin test. Middle Image: Skin lesions from C.
immitis infection, from http://drugster.info/img/ail/1899_1911_2.jpg. Right Image: Skin lesion
from C. immitis infection on face, courtesy of Glenn Bulmer.
Histoplasma capsulatum and Histoplasmosis
Histoplasmosis occurs in people and dogs, rarely has it occurred in other domestic or wild
animals. Infection occurs through inhalation of spores from this fungus. The history of this
disease is similar to that of coccidiomycosis. The first three cases of histoplasmosis was
described in the Panama Canal Zone in 1905 and 1906. The patients died of massive infections,
and in postmortem examination of diseased tissues, the disease was thought to have been caused
by a protozoan (Darling, 1906). Thus, the name H. capsulatum, which refers to what was
believed to be an encapsulated plasmodium found during the autopsy. The first case occurring in
the United States was recorded in 1926 and by 1934 only six cases had been described in
Panama and the United States, all postmortem.
Until 1940, Histoplasmosis was thought to be a rare and almost invariably fatal disease, and little
attention was paid to it. However, in 1940, many men who were given chest x-rays as part of
their physical examination to determine their fitness for military service, were found to have
calcified pulmonary lesions indicative of healed-over infections, which is normally a positive test
for tuberculosis. The incidence of these lesions were especially high in men from the Mississippi
and Ohio River valleys; few of these men tested positive for tuberculin test and so it was unlikely
that these lesions were due to tuberculosis infections. In 1945, HHiissttooppllaassmmiinn sskkiinn tteesstt revealed
that a large number of people in some areas of the United States tested positive for
Histoplasmosis, but appeared to be perfectly healthy; at some time in the past they had been
infected with Histoplasma capsulatum (Christie & Peterson, 1945). It was estimated that as
many as 20% of the population of the United States are or have been infected by this fungus. The
great majority of these either have no symptoms at all or suffer only miscellaneous aches and
pains, with a light cough, perhaps some dysentery, very much like symptoms of
coccidioidomycosis, flu, and various bacterial infections. The symptoms soon disappear and the
individual is then highly resistant or immune from further infection by this fungus.
However, again, in a small percentage of cases the fungus spreads, by way of the blood stream,
from the source of the original infection in the lungs throughout the body, and this may result in
massive infection that is usually rapid and fatal. Thus, the disease is very widespread, but until
1940, it was thought to be a rare, but fatal disease which was usually not diagnosed until an
autopsy was carried out and may not have been recognized even then. More cases probably
occurred, but because few pathologists were trained to recognize fungal diseases. Medical
mycology was still a little studied area at this time. As was the case in coccidioidomycosis, once
the disease has been disseminated from the lungs to the rest of the body, it is likely to be fatal
and nothing can be done.
Although there is a high incidence of this disease, it is not communicated from animal to animal
or person to person or even animal to people. It seems likely that the infection source is from the
soil where it has been demonstrated to exist as a saprobe. However, it apparently does not
sporulate in soil, but rather only in droppings of birds and bats. The fungus grows there and
presumably sporulates on the droppings. This is the reason that public parks throughout the
country do not allow people using the park to feed the birds. Large number of birds feeding in a
given area, where there are often a lot of people, would present an environment where there is
greater probability that someone may catch this disease.
Although this disease is little known, several years ago, on May 25, 1997, Bob Dylan was
hospitalized, with histoplasmosis, although his life was threatened, he apparently was never in
danger of dying of this disease. However, the disease became far better known after he
contracted it. I was still able to find a brief mention of this news story in the archives of the Los
Angeles Times. If you wish to read this article, click here.
Left Image: Histoplasmosis infection of gum, from
http://www.doctoribolit.ru/images/Histoplasmosis/Histoplasmosis04.gif. Right Image: Skin
lesion of upper lip due to histoplasmosis infection, from Centers for Disease Control and
Prevention's Public Health Image Library #6840.
Blastomyces and Blastomycosis
There are two species of this genus, Blastomyces dermatitidis and B. brasiliensis that occur in
North America and South America, respectively. These species occur naturally in soil, especially
soil in animal habitats. It is apparently widespread in Kentucky and Arkansas where infection in
dogs is common. Infection is rare in other animals, but have been recorded in cats, one horse and
one sea lion.
Infection apparently comes from spores or mycelium in the soil and any part of the body may be
invaded. Infections usually are first detected as skin lesions; the lesions may remain localized or
may gradually enlarge. In some case the fungus can spread throughout the whole body, resulting
in extensive ulceration. Males are infected more frequently than female - in some studies the
ratio is 15:1. There is no effective treatment.
Intermediate Infections
These are diseases that are intermediate between the first two categories. These fungal infections
may extend to a considerable depth within the tissue, but unlike the systemic diseases will not be
distributed to the rest of the body. One of the most common intermediate infection is Candida
albicans.
Candida albicans and Candidiasis
Candida albicans is a dimorphic fungus. That is, it grows as both mycelium and yeasts. This is
one reason why there were so many names given to this fungus. This fungus normally occurs in
the mouth, digestive tract, and vagina of perfectly healthy people, but under some circumstances,
and for reasons unknown, it may cause severe and even fatal infections, with lesions and
eruptions of the skin, nails, mouth, bronchial tubes and lungs. There are suggestions that there
are special strains of this species that are pathogenic. This is suggested by the fact that this
disease can be contagious and epidemics have occurred. Predisposition may also play a role in
infection. Oral infections known as thrush is relatively common. Infections can occur on various
parts of the body.
Candidiasis infections on various parts of body: Left Image: On tongue, commonly referred to as
Thrush. Middle Image: On neck. Right Image: Is a case where it is fatal. Lack of T-Cells allowed
infection to occur on many parts of body. Images courtesy of Glenn Bulmer, from
http://www.medicalmycology.net.
Chromoblastomycosis
Disease is mostly tropical to subtropical, but was first reported from Boston in 1915 and may be
caused by several species of fungi. Species causing this disease are mostly soil inhabiting or on
decaying vegetation and typically enter the foot or lower part of the leg through wounds from
walking bare-footed. Early treatment involves excision of infected area or cryosurgery. Chemical
treatments vary in their success of controlling this disease.
Left Image: Fonsecae pedrosoi infection of left leg. Right Image: Same leg after daily treatment
with Itraconazole. Images courtesy of Glenn Bulmer, from http://www.medicalmycology.net.
Aspergillus fumigatus and Aspergillosis
Aspergillus fumigatus is a species complex rather than a single species. It is actually composed
of ten species. These species are commonly found in decaying vegetation, especially when the
latter is undergoing microbiological heating, because this complex is thermophilic, adapted to
growing at high temperatures 50 - 55ºC (120 -130ºF).
Aspergillus fumigatus sometimes parasitizes animals, especially birds, infecting mainly lungs
and causing heavy mortality - up to 50% in young turkeys and up to 90% in young chicks. Heavy
losses have also been reported in herring gulls, ostriches and diving ducks in the wild and in
penguins in zoos. The fungus can also invade the embryos of eggs in incubators, and probably
does the same in eggs in nest in the wild. It also invade the uterus of pregnant cattle and grows
through the placenta into the fetus, which then dies and is aborted. It has been estimated that
64% of bovine abortion investigated were due to infection of A. fumigatus.
In people, the disease can lead to a chronic lung infection which is apparently very contagious.
The fungus is thought to cause death, but that is not certain. In patients that have died and A.
fumigatus has been isolated, many have also had underlying disease that possibly lowered their
resistance to the fungus. However, it is also possible that the fungus had lowered their resistance
to the other infective agents. It is difficult to know what came first.
REFERENCES
1. Anke T & Thines E. (2007) Fungal metabolites as lead structures for agriculture. In:
Exploitation of Fungi. Eds: Robson GD, van West P, Gadd GM. CUP.
2. Suryanarayanan TS et al (2009) Fungal endophytes and bioprospecting. Fungal Biology
Reviews 23, 9-19.
3. Wainwright M. (1995) An Introduction to Fungal Biotechnology. Wiley, Chichester.
4. Gow N. & Gadd G.M. (Eds)(1995) The Growing Fungus. Chapman Hall, London.
5. Pitt J.I. & Hocking A.D. (2009) Fungi and Food Spoilage (3rd edit). Springer.
6. Wainwright M. (1992) An Introduction to Fungal Biotechnology. Wiley, Chichester.
7. Young, Linda; Cauvain, Stanley P. (2007). Technology of Breadmaking. Berlin:
Springer. p. 79. ISBN 0-387-38563-0. The scientific name for baker's yeast is
Saccharomyces cerevisiae
8. Christie, A. & Peterson J. C. 1945. Pulmonary calcification in negative reactors to
tuberculin. Am J Public Health. 35:1131.
9. Darling, S.T. 1906. A protozoan general infection producing pseudo tubercles in the
lungs and focal necrosis in the liver, spleen and lymph nodes. JAMA 46,1283-1285
10. Dickson, E. C. 1937. "Valley fever" of the San Joaquin Vallen and fungus Coccidioides.
California West. Med., 47: 151-155.
11. Dickson, E. C., & Gifford, M. A. 1938. Coccidioides infection (Coccidioidomycosis): the
primary type of infection. Arch. Intern. Med., 62: 853-871.
12. Edwards, L. B., & Palmer, C. 1957. Prevalence of sensitivity to coccidioidin, with special
reference to specific and non-specific reactions to coccidioidin and histoplasmin. Dis.
Chest. 31: 35-60.
13. Fiese, M. J. 1958, Coccidioidomycosis. Charles C. Thomas, Springfield, IL, 253 p.
14. Hawksworth, D. L. 1992. Fungi: A neglected component of biodiversity crucial to
ecosystem function and maintenance. Canadian Biodiversity 1: 4-10.
15. Hudler, G. W. 1998. Magical Mushrooms, Mischievous Molds. Princeton University
Press. Princeton, New Jersey, 248 p.
16. Lacaz, C. da S., E.M. Heins-Vaccari, N. Takahashi de Melo, and G.L. Hernandez-
Arriagada. 1996. Basidiomycosis: a review of the literature. Rev. Inst. Med. Trop. S.
Paulo, 38(5): 379-390.
17. Speller, D.C.E. and A. G. MacIver. 1970. Endocarditis caused by a Coprinus species: A
fungus of the toadstool group. J. Med. Microbiol. 4:370-374
18. Kern, M.E. and F.A. Uecker. 1986. Maxillary Sinus Infection Caused by the
Homobasidiomycetous Fungus Schizophyllum commune. Journal of Clinical
Microbiology. 23: 1001-1005.
19. Rippon, J. W. 1988. Medical Mycology: The Pathogenic Fungi and the Pathogenic
Actinomycetes. W. B. Saunders Company Harcourt Brace Jovanovich, Inc. Philadelphia,
PA, 797 p.

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Economic and practical food and beverage, Health applications of mycology

  • 1. NAME: WASWA WALTER WAKHUNGU UNIVERSITY: PWANI UNIVERSITY ADM.NO. : SG26/PU/36067/16 COURSE: MASTERS OF SCIENCE [MICROBIOLOGY] DEPARTMENT: BIOLOGICAL SCIENCE SCHOOL: SCHOOL OF PURE AND APPLIED UNIT: ADVANCED MYCOLOGY UNIT CODE: SBT G805 LECTURER: DR. JOYCE JEFWA ASSIGNMENT: Economic and practical food and beverage, Health applications of mycology A. Food sources B. Fermenters C. Wine And Beer Making D. Leavening Agent E. Natural Food Flavor And Color F. Drugs G. Human Disease Date : 24/11/2016
  • 2. A. FOOD 1. Protein source A large range of edible fungi are cultured. Agaricius bisporus is cultivated widely in western countries. In addition, Shii-take (Lentinus edodes), Straw mushroom (Flammulina velutipes), Oyster mushroom (Pleurotus ostreatus), and Chinese Black mushroom (Auricularia polytricha) are cultured in various Asian countries, and increasingly in western countries. The truffle industry is economically important in southern Europe and production is expanding in the southern hemisphere. Finally, edible mushrooms are picked from the wild, especially in Europe. Many of the fungi are eaten fresh, but there is also a market for dried mushrooms and canned truffles. Fungi are ideal food becoming an ideal source of myco-protein , healthy alternative to meat. They have a fairly high content of protein (typically 20-30% dry matter as crude protein) which contains all of the essential amino acids. Fungal biomass is also a source of dietary fibre, and is virtually free of cholesterol. Mushrooms are cultivated around the world, global annual production being in the region of 8 million metric tones eg Agaricus spp, the mycelium of a species of Fusarium.
  • 3. The morel is not commonly seen in shops. The ascocarp is hollow and delicate. The structure is pointed and rarely higher than 10cm. © Dave Powell , USDA Forest Service. Image 0808042. http://www.ipmimages.org. Pleurotus ostreatus, also known as Oyster mushroom. © Robert L. Anderson, USDA Forest Service. Image 0590031. http://www.ipmimages.org.
  • 4. Fruiting body of Auricularia. This fungus is found on the dying branches of trees throughout the University grounds. B. FERMENTER 1. Soy Sauce We tend to take a variety of foods and food additives for granted, without being aware of the processes which get them to the table. One such food is Soy Sauce and its partner bean curd. Soy sauce (shoyu) is a dark brown, salty liquid, high in amino acids and with a meat-like flavour. It was first produced in Japan (a similar product is made in other east Asian countries), where
  • 5. some microbial cultures were used to ferment the unpalatable soy beans. The current industrial process is highly controlled, used around the world and is based on this original process. Fermentation is in two stages. Initially, soy beans are soaked, cooked to remove contaminants, and then mixed with roasted wheat. The fungus Aspergillus oryzae is added to the mix, and the amended mix kept aerobically for 20 to 40 hours at 25 C. The fungus produces invertases, amylases and cellulases, which degrade the soy paste. The paste is then mixed and taken into the second phase of fermentation. In deep vats, brine is added to the paste and the yeast Saccharomyces rouxii and lactobacilli are added. Anaerobic conditions develop quickly, preventing further growth of A. oryzae. After about a month, a sour liquid is apparent. The liquid contains large concentrations of amino acids, simple sugars and a range of vitamins. After separation and further storage, the liquid is sterilised, bottled and sold as Soy Sauce. Similar products are called Koji, Idli, Patu, Laochao or Ogi. 2. Cheese Production of cheese relies on diverse microbes. The cheese environment is dynamic and the specific biological interactions complex. Fungi play a role in ripening in two different ways: they may assist ripening from the outside of the cheese, and they can impart flavours from inside the cheese. Various yeast and filamentous fungi colonise the surface of cheeses. The may be surface contaminants or deliberately inoculated. Their impact will rely on the temperature, water content, pH, salinity and redox of the substrate.
  • 6. Soft-ripened cheeses are ripened from the outside in. Penicillium camemberti (=P candidum) is inoculated onto the surface of cheeses, typically Brie, Camembert and Neufchatel, where growth over 7 to 70 days imparts a flexible powdery white crust and contributes to the runny texture and intense flavours of the contents. Various cheeses are sold that have been stab-inoculated with a strain of Penicillium roquefortii. The result is a blue streak or vein through the cheese. The fungus imparts a strong, pungent flavour due to the aerobic production of methyl ketones. Famous blue cheeses include: Roquefort, Gorgonzola, Stilton, and Danish Blue. The fungus is a widespread spoilage organism found in cool conditions. It can grow at low oxygen availability and tolerates acidic conditions. Thus the presence of blue cheeses in your fridge may lead to widespread contamination of products like bread that use acids as preservatives. Cheese is susceptible to the growth of fungi. While a huge diversity are associated with unwanted contamination, some such as Geotrichum candidum have been expoited because they are thought to impart desirable flavours and assist with the ripening process. Wine and BeerMaking Although there is a distinction between beer, wine and liquor as well as other lesser known alcoholic beverages, they share one thing in common. They are the fermentation products of yeasts, mostly Saccharomyces cerevisiae or in the case of beers, usually S. carlsburgiensis. Yeasts, as you recall, are not mycelial. They are unicellular fungi that reproduce asexually by budding or fission. The reaction by which alcoholic beverages are produced is generally referred to as fermentation and may be summarized as:
  • 7. Yeast + Glucose è Alcohol (Ethanol) + CO2 This reaction is also important in baking bread, but the desired product is then the carbon dioxide rather than alcohol. The production of alcohol occurs best in the absence of oxygen. However, from the yeast's point of view, alcohol and carbon dioxide are waste products, and as the yeast continues to grow and metabolize in the sugar solution, the accumulation of alcohol will become toxic when it reaches a concentration between 14-18%, thereby killing the yeast cells. This is the reason why the percentage of alcohol in wine and beer can only be approximately 16%. In order to produce beverages (liquor) with higher concentrations of alcohol, the fermented products must be distilled. With the genetic manipulation of yeasts, numerous varietal strains have been bred. This, along with modifications in the brewing process have led to different types of beers. Those most often seen in North America include:  Lager. Beers made with yeast that settle on the bottom (Saccharomyces carlsbergensis) of the container used. Thus, all the yeast and other material settles on the bottom which results in a clear beer. Most American beers are lagers. o Pilsner. A colorless lager beer originally brewed in the city of Pilsen. Water used for this style of beer tend to be harder, with a higher calcium and magnesium content than water used for lager. The color of pilsner is also lighter than that of lager beer.  Ale. Beers made with yeast that floats (Saccharomyces cerevisiae) to the top of the brewing vats, resulting in a cloudier beer. They tend to have a higher alcohol content than lagers.
  • 8. o Stout. A very dark, almost black ale. The dark color and roasted flavor is derived from the roasted barley, and/or roasted malt. Beer historians consider it to be the descendant of the Porter ale. o Porter. A very dark ale. The darker color and special flavor comes from toasting the malt before brewing. This usually results in a stronger taste and higher alcohol content. Considered by beer historians to have evolved into the Stout ale. C. LEAVENING AGENT Baker's yeast is the common name for the strains of yeast commonly used as a leavening agent in baking bread and bakery products, where it converts the fermentable sugars present in the dough into carbon dioxide and ethanol. Baker's yeast is of the species Saccharomyces cerevisiae D. FOOD ODOR AND FLAVOR AND FLAVOR Fungus is primarily responsible for the production of some characteristic odour, flavour, or texture and may or may not become part of the final edible product. Growing filamentous fungi on water-soakedseeds of plants is the basis for production of several human food products in Asia, including soy sauce and various other fermented foods. In soy sauce production soybeans are soaked, cooked, mashed and fermented with Aspergillus oryzae and A. sojae. Depending on the size of the factory, the soybeans may be fermented in fist-sized balls (the traditional method) or on trays. When the substrate has become overgrown with the fungus the material is mixed
  • 9. with salt and water and the fermentation is completed in the brine. The biggest industrial units today use a continuous process in which defatted soybean flakes, moistened and autoclaved are mixed with ground, roasted wheat. The mixture is turned mechanically to ensure even growth of Aspergillus oryzae and A.sojae for two to three days; then it is transferred to brine and inoculated with Pediococcus halophilus and 30 days later with Saccharomyces rouxii. The brine fermentation takes six to nine months to complete, after which the soy sauce is pressure-filtered, pasteurised and bottled. While many flavours are produced by bacteria, fungi are responsible for a range of flavours including terpenes, menthol and lactones. Fungi also produce compounds that deodorise offensive and neutralise bitter flavours. At present, flavour enhancement is an unimportant area of the industrial use of fungi. Colours Fungi produce a range of compounds that alter the colour of food. For instance, Monoascus purpureus has been traditionally used for the production of red wine. The pigments are polyketides that are insoluble in acid conditions. Beta carotene is produced by a range of Mucorales. This can be added to a variety of foods. Concern with the potentially toxic or allergic characteristics of some artificial colours has led to a closer examination of colours from natural sources. E. DRUGS
  • 10. Fungi make an extraordinarily important contribution to managing disease in humans and other animals. At the beginning of the 21st century, Fungi were involved in the industrial processing of more than 10 of the 20 most profitable products used in human medicine. Two anti-cholesterol statins, the antibiotic penicillin and the immunosuppressant cyclosporin A are among the top 10. Each of these has a turn over in excess of $1 billion annually. Drug discovery continues. The following have recently been approved for human use: Micafungin is an antifungal agent; mycophenolate is used to prevent tissue rejection; rosuvastatin is usd to reduce cholesterol; and cefditoren as an antibiotic Antibiotics From Fungi In 1941, penicillin from the fungus Penicillium chrysogenum was first used successfully to treat an infection caused by a bacterium. Use of penicilin revolutionised the treatment of pathogenic disease. Many formally fatal diseases caused by bacteria became treatable, and new forms of medical intervention were possible. When penicillin was first produced, the concentration of active ingredient was approximately 1 microgram per ml of broth solution. Today, improved strains and highly developed fermentation technologies produce more than 700 micrograms per ml of active ingredient. In the early broths, several closely related molecules were present. These molecules are beta lactam rings fused to five-membered thiazolidine rings, with a side chain. The side chain can be chemically modified to provide slightly different properties to the compound. The natural penicillins have a number of disadvantages. They are destroyed in the acid stomach, and so cannot be used orally. They are sensitive to beta lactamases, which are produced by resistant bacteria, thus reducing their effectiveness. Also, they only act on gram positive bacteria.
  • 11. Modifications to manufacturing conditions have resulted in the development of oral forms. However, antibiotic resistance among bacteria is becoming an extremely important aspect determining the long-term use of all antibiotics. Cephalosporins also contain the beta lactam ring. The original fungus found to produce the compounds was a Cephalosporium, hence the name. As with penicillin, the cephalosporin antibiotics have a number of disadvantages. Industrial modification of the active ingredients has reduced these problems. The only broadly useful antifungal agent from fungi is griseofulvin. The original source was Penicillium griseofulvin. Griseofulvin is fungistatic, rather than fungicidal. It is used for the treatment of dermatophytes, as it accumulates in the hair and skin following topical application. More recently, several new groups have been developed. Strobilurins target the ubihydroquinone oxidation centre, and in mammals, the compound from fungi is immediately excreted. Basidiomycetes, especially from tropical regions, produce an enormous diversity of these compounds. Sordarins are structurally complex molecules that show a remarkably narrow range of action against yeasts and yeast-like fungi. The compounds inhibit protein biosynthesis and so may become important agents against a number of fungal pathogens of humans. Echinocandins are cyclic peptides with a long fatty acid side chain. They target cell wall formation. Semi-synthetic members of the group of compounds include pneumocandins which are in use in humans.
  • 12. Immune Suppressants Cyclosporin A is a primary metabolite of several fungi, including Trichoderma polysporum and Cylindrocarpon lucidum. Cyclosporin A has proven to be a powerful immunosuppressant in mammals, being widely used during and after bone marrow and organ transplants in humans. Cyclosporin A is a cyclic peptide consisting of 11 mainly hydrophobic amino acids. Its inhibition of lymphocytes was first discovered during the 1970s. Subsequently, the mode of action was elucidated. Cyclosporin A binds to a cytosolic protein called cyclophilin. Cyclophilin is found amongst many different organisms and its form appears highly conserved. Cyclophilin is involved with folding the protein ribonuclease. However, the Cyclosporin A/cyclophilin complex also binds to calcineurin. Calcineurin dephosphorylates a transcription factor, thereby triggering transcription of numerous genes associated with T cell proliferation. When the complex binds to calcineurin, T cell proliferation is suppressed. The inhibition of T cells proliferation results in the suppression of the activation process associated with invasion by foreign bodies. As a consequence, transplant tissues, which are foreign bodies, are not rejected. Calcineurin is also highly conserved amongst phylogenetically diverse organisms. In fungi such as the human pathogen Cryptococcus neoformans, calcineurin is necessary for recovery from cell cycle arrest, growth in hypertonic solutions and regulation of the calcium pump. Thus the interaction of the Cyclosporin A/cyclophilin complex with calcineurin in Cryptococcus will result in death of the pathogen. However, in humans, cyclosporin also suppresses the immune system. The side effect is an unacceptable risk, and Cyclosporin A is not used as a fungicide in humans at present.
  • 13. Gliotoxins also have immunological and antibiotic activity. Produced by many fungi including Aspergillus fumigatus, gliotoxins belong to a class of compounds called epipolythiodioxopiperazines. The antibiotic activity is widely recognised and considered uninteresting. However, its effect on the immune system, especially macrophages, is being re- examined. A wide range of other compounds with antibiotic activity are also known. They have been rejected for use in medicine because of unwanted side effects, or instability of the active compound. Ergot Alkaloids Claviceps purpurea is the causal agent of St Anthonies fire, a scourge of the middle ages when ergots contaminated flour. The ergots contain many alkaloids. Their effects are quite variable. They act on the sympathetic nervous system resulting in the inhibition of noradrenaline and sclerotin, causing dilation of blood vessels. They also act directly on the smooth muscles of the uterus causing contractions, thus their early use to induce abortion. Their strongest effect is intoxication, caused by lysergic acid amides, one of which is the recreational (and illegal) drug, LSD.
  • 14. Seeds of Paspalum replaced by C. paspalli. Ergot alkaloids have a number of medicinal uses. Perhaps the most widespread use is in the treatment of migraines. The vasodilator activity reduces tension during an attack. The drugs also reduce blood pressure, though with untoward side effects. Alkaloids are now produced in culture by strains of C. fusiformis and C. paspalii. Statins Aspergillus terreus, a soil-borne fungus, produces a secondary metabolite called lovastatin and Phoma sp produces squalestatin. Statins have been used to reduce or remove low density lipoproteins from blood vessels in humans. In fact, the compounds all act via an enzyme in the liver that makes cholesterol, lovastatin inhibits HMG CoA reductase and squalestatin inhibits squalene synthase. By blocking the enzyme, the body removes cholesterol complexes from the inside of blood vessels. This has the effect of reducing or removing blockages in arteries, and thereby reducing the chance of a heart attack, strokes and diabetes. In addition, statins have been implicated in attracting stem cells to damaged tissues. The stem cells then appear to regenerate the tissue.
  • 15. Some statins induce problems. One form of the drug has been associated with muscle wastage. Others appear to lack side effects and have been recommended for wide spread use to control heart disease. F. FUNGAL DISEASES IN HUMANS According to CDC fungi are everywhere. There are approximately 1.5 million different species of fungi on Earth, but only about 300 of those are known to make people sick. Fungal diseases are often caused by fungi that are common in the environment. Fungi live outdoors in soil and on plants and trees as well as on many indoor surfaces and on human skin. Most fungi are not dangerous, but some types can be harmful to health.In discussing fungal diseases, the most convenient way of classifying them is to categorize them according to the type of infection that has occurred: 1. Superficial infections, are caused by fungi that attack the skin or its appendages (nail, feathers and hair). Some examples of these infection include ringworms, jock-itch and athlete's foot. These fungi are known as dermatophytes. 2. Systemic infections, diseases that occur deep within the tissues, involving vital organs and/or the nervous system, and which may be fatal, but may also be chronic. Entry into the body is usually through inhalation of spores or open wounds. Blood circulation or respiratory system may then transmit fungus
  • 16. throughout body and additional infection of internal organ may occur. These fungi, are usually saprotrophic fungi, growing in the soil. A third, Intermediate infection, is sometimes also recognize and is intermediate between the two just discussed. The infection will occur below the skin, but will remain localized Superficial Infections The superficial mycoses are the most well known since they can be readily observed. They commonly occur on the hair, nails and skin of infected individuals. They have been recorded in various compilations of medical literature for well over a thousand years as ring worm, athlete's foot, jock itch and piedra. For each type of infection, there can also be a variety of species that may be causing the disease. Thus, we will only have a general discussion on this group of diseases. Ringworm and RelatedDermatophytes Ringworm usually occurs on the exposed parts of the body, forming circular growths that may appear darker or lighter than the normal skin color, with symptoms that include skin lesion, rash and itching of the infected area. Ringworm infections are common where conditions are unsanitary and crowded with people and has been known since early historical time. There are indications that ringworm was more prevalent in the recent past than now because of improvements in sanitary conditions and health habits. The Greeks called it Herpes (=circular or ring form) and the Romans associated the disease with the larval stage of Tinea, the genus for clothes moth. The two names were eventually combined to "ringworm". Although the actual cause of ringworm was not known until the early 1800s, the practice of segregating infected
  • 17. individuals to prevent spread of the disease indicated that there was knowledge that this disease was contagious and prevalent, and could be passed from person to person was known prior to the cause of infection. It was Gruby that isolated and described one of the ringworm fungi, Trichophyton, meaning "thread plant", and through inoculation on healthy parts of the scalp, was able to reproduce the disease. He also carried out the same experiment with several other human pathogenic fungi and inoculated himself with the pathogen, as well as others. Although this was a great accomplishment, Gruby also had a great deal of luck since, at the time, isolation of specific fungi was not common practice, and this was also 30 years prior to the development of techniques to grow fungi and bacteria in pure culture. According to Ainsworth, more than 350 species of dermatophytes have been proposed and given approximately 1,000 names, which has caused some confusion in medical mycology. The proliferation in names have come about because different researchers have worked with the same species of a pathogen, in a different place and time, and each were familiar with that particular isolate of that particular species of fungus and probably not too familiar with that isolate. They grew it in culture briefly and published on it. Thus, each newly isolated dermatophytic fungus was given a name, sometimes according to the symptoms with which it was associated or according to the part of the body affected, i.e. top of the head, neck, face, hand, arm, leg and foot, or even the geographical region, or sometimes just for the sake of publication (due to the competitiveness of medical schools) . This led to a great deal of confusion in the understanding of mycoses.
  • 18. Although the first species were described in the 1840s, they were little studied until the 1940s, when the United States military personnel, while fighting in the South Pacific, during WWII, contracted ringworm and other fungi in the humid tropics (an example of advancement of knowledge due to driven research). This led to an intensive study, by the government of such fungi with many species being reduced to synonyms. For example, 172 species were reduced to Candida albicans. Epidemiology of Ringworm Fungi that cause ringworm are widespread, geographically, and usually not of major concern, other than as cosmetic problems. However, cases in which these diseases cause extreme disfigurements and infections are known to occur, but are rare outside of the tropics, and are believed to be due to poor diet and unsanitary condition (Christensen, 1965). At one time ringworm was a common disease, particularly of children of poorer classes. The inferences usually is that this was mainly a matter of such children being exposed to less soap and water than were children of the well-to-do. It is probable that deficiency in diet may also have made them more susceptible. There have been epidemics of ringworm that have developed in many cities in the United States. Several species of fungi that cause ringworm are common on adults, and it seems highly probable that some of them are regularly present without causing any obvious symptoms. Species that cause ringworm belong to the genera Trichophyton and Microsporum. These genera of fungi are somewhat unusual in that they produce asexual spores, but not sexual spores or at least produce them so infrequently that they have not been observed. Species of fungi causing ringworm can be ecologically divided into three groups:
  • 19. 1. Zoophilic or "animal loving." Species infect animals primarily, e.g. cats, dogs, horses, cows, poultry, but can readily be transmitted to people. This is probably the most common source of ringworm in people, and is usually caused by Microsporum canis, a species usually found on cats and dogs. Animals that are carriers of ringworm do not necessarily show outward signs of the disease. Symptomless animals and probably people as well are carriers of these diseases. The infections are spread mainly by spores, but mycelial fragment in skin and hair can presumably also occur. Spores are very long lived and can remain alive for years in blankets, in clothing, bedding, combs and other grooming tools. 2. Anthropophilic or "man loving." Species infect people and cannot be transferred to animals. 3. Geophilic or "earth loving." Species occur naturally in soil, presumably as a saprobe, but is capable of infecting animals and people. Another words these are facultative parasites! There must be great differences among individuals in susceptibility to infection of these ringworm fungi as well as great differences in susceptibility of an individuals at different times. There are many questions that remain unanswered concerning this species causing the various forms of ringworm. Ringworm infections are conveniently divided into categories, based on the part of the body that was infected:  Tinea capitis: Ringworm of the scalp, eyebrow and lashes.  Tinea corporis: Ringworm of the body.
  • 20.  Tinea cruris: Ringworm of the groin, perineum and perianal region. Infections are commonly referred to as "jock itch".  Tinea unguium: Ringworm of the nail.  Tinea barbae: Ringworm of the beard.  Tinea pedis: Ringworm of the feet. Infections are commonly referred to as athlete's foot.  Tinea manuum: Ringworm of the hand. Left Image: Example of Tinea capitis. Middle Image: Example of Tinea corporis. Right Image: Example of Tinea pedis (Athlete's Foot). All images courtesy of Dr. Glenn Bulmer, from http://www.medicalmycology.net. Note that the various "Tinea" names given to the various forms of ringworms do not constitute species names. A summary of the above ringworm diseases, based on anatomical locations can be found on the Medline Plus Health Information. There is also discussion on treatment for the various types of ringworms that have been omitted on this web page. Warning, this site has very explicit graphics of these diseases!
  • 21. Presumably infection is spread mainly by air-borne spores which is why veterinarians do not want ring-worm infected animals to remain in their clinics or hospitals. If this is the case, all of us at one time must be exposed to infections by various ringworm fungi. Why is it then that few of us become infected? Why is infection usually localized, e.g. ringworm of the scalp only occurs in part while most areas are not affected? Surely, there are enough spores produced that the entire scalp will be infected. Sometimes one person in a family, or animal in a herd, will get ringworm and it will not spread to others, whereas other times it is highly contagious. There is a great deal to be learned about ringworm. An interesting disease that is not one of the ringworms is piedra. This is a disease of the hair where mycelium grows along the shaft of the hair and often fuses clumps of hair together. Usually occurs in unsanitary conditions, in tropical countries. To treat piedra the infected hair is cut or shaved and a topical azole cream, salycylic acid or 2% formaldehyde is applied to the affected area. Systemic or Deep-SeatedMycoses There are a dozen or more species of fungi causing various systemic or deep-seated mycoses in man and animals. We will discuss several of the more prevalent species or because of some interesting aspect of the fungus or disease. Coccidioides immitis, the cause of Coccidioidomycosis (Valley Fever) This species is endemic to the southwest, in the United States (California, eastward through Arizona, New Mexico, and western half of Texas), Northern Mexico and some areas of Central and South America. In the United States, it is most commonly recorded from Kern County, in the
  • 22. San Joaquin Valley of California. Infection may occur following travel to one of the endemic areas. The first case of coccidioidomycosis was described in Argentina shortly before 1890; the patient suffered for seven years before finally dying and by 1915, there were 40 known cases of this disease, which was thought to be a rare and universally fatal. However, by this time it was already known that there was a disease called Valley Fever, which was not associated, at that time, with C. immitis. It would not be until Dickson (1937) that it was realized that Valley Fever was just a milder form of coccidioidomycosis. Dickson & Gifford (1938) carrying out ccoocccciiddiiooiiddiinn skin test of long time residents of Kern County demonstrated that 50-70% have, at some time been infected by this fungus. The test is like a tuberculosis (TB) test where substances called antigens that are associated with the disease are injected just below the skin, of your forearm, and the results read 24 to 48 hours later. If an infection of C. immitis has occurred, antibodies will be produced by the body that will react with the antigen that has been injected, causing a large red swelling in the area of the injection. Coccidioides immitis is contracted by inhalation of spores and primarily causes a respiratory disease in animals and people, but from the lungs it may spread throughout the body by way of the bloodstream and cause pathologic changes - skin lesions of one sort or another - in just about all tissues in all parts of the body. In the usual course of events, infection results in a more or less acute but benign and self-limiting respiratory disease, but once the patient recovers from this, they are likely to be permanently immune from further infection. Fiese (1958), an authority on this disease, says that about 60% of those infected have few or no symptoms, and 40% have symptoms of varying degrees of severity; chills, fever, chest pains, coughing, lassitude - symptoms typical of a dozen other infections as well. These symptoms develop ten to fourteen days after infection, and may persist for some time, but eventually, in most cases, the
  • 23. immunological processes of the body take over and rids it of infection, although lesions and scars in the lungs may remain. In a relatively few cases (1 in 500) the fungus is disseminated from the lungs to other parts of the body, and this secondary stage may result in severe lesions in the skin, bones, and internal organs and the victim will have massive external and internal lesions and abscesses. If this stage is reached, it is unlikely that the victim will recover, death will occur within weeks or after a long and lingering illness. Sometime the disease proceeds to a fairly advanced stage and then remains static for years, and it may regress and later reappear. Amphotericin B is the drug of choice to treat this disease. Left Image: Positive reaction to coccidioidin skin test. Middle Image: Skin lesions from C. immitis infection, from http://drugster.info/img/ail/1899_1911_2.jpg. Right Image: Skin lesion from C. immitis infection on face, courtesy of Glenn Bulmer. Histoplasma capsulatum and Histoplasmosis
  • 24. Histoplasmosis occurs in people and dogs, rarely has it occurred in other domestic or wild animals. Infection occurs through inhalation of spores from this fungus. The history of this disease is similar to that of coccidiomycosis. The first three cases of histoplasmosis was described in the Panama Canal Zone in 1905 and 1906. The patients died of massive infections, and in postmortem examination of diseased tissues, the disease was thought to have been caused by a protozoan (Darling, 1906). Thus, the name H. capsulatum, which refers to what was believed to be an encapsulated plasmodium found during the autopsy. The first case occurring in the United States was recorded in 1926 and by 1934 only six cases had been described in Panama and the United States, all postmortem. Until 1940, Histoplasmosis was thought to be a rare and almost invariably fatal disease, and little attention was paid to it. However, in 1940, many men who were given chest x-rays as part of their physical examination to determine their fitness for military service, were found to have calcified pulmonary lesions indicative of healed-over infections, which is normally a positive test for tuberculosis. The incidence of these lesions were especially high in men from the Mississippi and Ohio River valleys; few of these men tested positive for tuberculin test and so it was unlikely that these lesions were due to tuberculosis infections. In 1945, HHiissttooppllaassmmiinn sskkiinn tteesstt revealed that a large number of people in some areas of the United States tested positive for Histoplasmosis, but appeared to be perfectly healthy; at some time in the past they had been infected with Histoplasma capsulatum (Christie & Peterson, 1945). It was estimated that as many as 20% of the population of the United States are or have been infected by this fungus. The great majority of these either have no symptoms at all or suffer only miscellaneous aches and pains, with a light cough, perhaps some dysentery, very much like symptoms of
  • 25. coccidioidomycosis, flu, and various bacterial infections. The symptoms soon disappear and the individual is then highly resistant or immune from further infection by this fungus. However, again, in a small percentage of cases the fungus spreads, by way of the blood stream, from the source of the original infection in the lungs throughout the body, and this may result in massive infection that is usually rapid and fatal. Thus, the disease is very widespread, but until 1940, it was thought to be a rare, but fatal disease which was usually not diagnosed until an autopsy was carried out and may not have been recognized even then. More cases probably occurred, but because few pathologists were trained to recognize fungal diseases. Medical mycology was still a little studied area at this time. As was the case in coccidioidomycosis, once the disease has been disseminated from the lungs to the rest of the body, it is likely to be fatal and nothing can be done. Although there is a high incidence of this disease, it is not communicated from animal to animal or person to person or even animal to people. It seems likely that the infection source is from the soil where it has been demonstrated to exist as a saprobe. However, it apparently does not sporulate in soil, but rather only in droppings of birds and bats. The fungus grows there and presumably sporulates on the droppings. This is the reason that public parks throughout the country do not allow people using the park to feed the birds. Large number of birds feeding in a given area, where there are often a lot of people, would present an environment where there is greater probability that someone may catch this disease. Although this disease is little known, several years ago, on May 25, 1997, Bob Dylan was hospitalized, with histoplasmosis, although his life was threatened, he apparently was never in danger of dying of this disease. However, the disease became far better known after he
  • 26. contracted it. I was still able to find a brief mention of this news story in the archives of the Los Angeles Times. If you wish to read this article, click here. Left Image: Histoplasmosis infection of gum, from http://www.doctoribolit.ru/images/Histoplasmosis/Histoplasmosis04.gif. Right Image: Skin lesion of upper lip due to histoplasmosis infection, from Centers for Disease Control and Prevention's Public Health Image Library #6840. Blastomyces and Blastomycosis There are two species of this genus, Blastomyces dermatitidis and B. brasiliensis that occur in North America and South America, respectively. These species occur naturally in soil, especially soil in animal habitats. It is apparently widespread in Kentucky and Arkansas where infection in dogs is common. Infection is rare in other animals, but have been recorded in cats, one horse and one sea lion.
  • 27. Infection apparently comes from spores or mycelium in the soil and any part of the body may be invaded. Infections usually are first detected as skin lesions; the lesions may remain localized or may gradually enlarge. In some case the fungus can spread throughout the whole body, resulting in extensive ulceration. Males are infected more frequently than female - in some studies the ratio is 15:1. There is no effective treatment. Intermediate Infections These are diseases that are intermediate between the first two categories. These fungal infections may extend to a considerable depth within the tissue, but unlike the systemic diseases will not be distributed to the rest of the body. One of the most common intermediate infection is Candida albicans. Candida albicans and Candidiasis Candida albicans is a dimorphic fungus. That is, it grows as both mycelium and yeasts. This is one reason why there were so many names given to this fungus. This fungus normally occurs in the mouth, digestive tract, and vagina of perfectly healthy people, but under some circumstances, and for reasons unknown, it may cause severe and even fatal infections, with lesions and eruptions of the skin, nails, mouth, bronchial tubes and lungs. There are suggestions that there are special strains of this species that are pathogenic. This is suggested by the fact that this disease can be contagious and epidemics have occurred. Predisposition may also play a role in infection. Oral infections known as thrush is relatively common. Infections can occur on various parts of the body.
  • 28. Candidiasis infections on various parts of body: Left Image: On tongue, commonly referred to as Thrush. Middle Image: On neck. Right Image: Is a case where it is fatal. Lack of T-Cells allowed infection to occur on many parts of body. Images courtesy of Glenn Bulmer, from http://www.medicalmycology.net. Chromoblastomycosis Disease is mostly tropical to subtropical, but was first reported from Boston in 1915 and may be caused by several species of fungi. Species causing this disease are mostly soil inhabiting or on decaying vegetation and typically enter the foot or lower part of the leg through wounds from walking bare-footed. Early treatment involves excision of infected area or cryosurgery. Chemical treatments vary in their success of controlling this disease.
  • 29. Left Image: Fonsecae pedrosoi infection of left leg. Right Image: Same leg after daily treatment with Itraconazole. Images courtesy of Glenn Bulmer, from http://www.medicalmycology.net. Aspergillus fumigatus and Aspergillosis Aspergillus fumigatus is a species complex rather than a single species. It is actually composed of ten species. These species are commonly found in decaying vegetation, especially when the latter is undergoing microbiological heating, because this complex is thermophilic, adapted to growing at high temperatures 50 - 55ºC (120 -130ºF).
  • 30. Aspergillus fumigatus sometimes parasitizes animals, especially birds, infecting mainly lungs and causing heavy mortality - up to 50% in young turkeys and up to 90% in young chicks. Heavy losses have also been reported in herring gulls, ostriches and diving ducks in the wild and in penguins in zoos. The fungus can also invade the embryos of eggs in incubators, and probably does the same in eggs in nest in the wild. It also invade the uterus of pregnant cattle and grows through the placenta into the fetus, which then dies and is aborted. It has been estimated that 64% of bovine abortion investigated were due to infection of A. fumigatus. In people, the disease can lead to a chronic lung infection which is apparently very contagious. The fungus is thought to cause death, but that is not certain. In patients that have died and A. fumigatus has been isolated, many have also had underlying disease that possibly lowered their resistance to the fungus. However, it is also possible that the fungus had lowered their resistance to the other infective agents. It is difficult to know what came first. REFERENCES 1. Anke T & Thines E. (2007) Fungal metabolites as lead structures for agriculture. In: Exploitation of Fungi. Eds: Robson GD, van West P, Gadd GM. CUP. 2. Suryanarayanan TS et al (2009) Fungal endophytes and bioprospecting. Fungal Biology Reviews 23, 9-19. 3. Wainwright M. (1995) An Introduction to Fungal Biotechnology. Wiley, Chichester. 4. Gow N. & Gadd G.M. (Eds)(1995) The Growing Fungus. Chapman Hall, London. 5. Pitt J.I. & Hocking A.D. (2009) Fungi and Food Spoilage (3rd edit). Springer.
  • 31. 6. Wainwright M. (1992) An Introduction to Fungal Biotechnology. Wiley, Chichester. 7. Young, Linda; Cauvain, Stanley P. (2007). Technology of Breadmaking. Berlin: Springer. p. 79. ISBN 0-387-38563-0. The scientific name for baker's yeast is Saccharomyces cerevisiae 8. Christie, A. & Peterson J. C. 1945. Pulmonary calcification in negative reactors to tuberculin. Am J Public Health. 35:1131. 9. Darling, S.T. 1906. A protozoan general infection producing pseudo tubercles in the lungs and focal necrosis in the liver, spleen and lymph nodes. JAMA 46,1283-1285 10. Dickson, E. C. 1937. "Valley fever" of the San Joaquin Vallen and fungus Coccidioides. California West. Med., 47: 151-155. 11. Dickson, E. C., & Gifford, M. A. 1938. Coccidioides infection (Coccidioidomycosis): the primary type of infection. Arch. Intern. Med., 62: 853-871. 12. Edwards, L. B., & Palmer, C. 1957. Prevalence of sensitivity to coccidioidin, with special reference to specific and non-specific reactions to coccidioidin and histoplasmin. Dis. Chest. 31: 35-60. 13. Fiese, M. J. 1958, Coccidioidomycosis. Charles C. Thomas, Springfield, IL, 253 p. 14. Hawksworth, D. L. 1992. Fungi: A neglected component of biodiversity crucial to ecosystem function and maintenance. Canadian Biodiversity 1: 4-10. 15. Hudler, G. W. 1998. Magical Mushrooms, Mischievous Molds. Princeton University Press. Princeton, New Jersey, 248 p.
  • 32. 16. Lacaz, C. da S., E.M. Heins-Vaccari, N. Takahashi de Melo, and G.L. Hernandez- Arriagada. 1996. Basidiomycosis: a review of the literature. Rev. Inst. Med. Trop. S. Paulo, 38(5): 379-390. 17. Speller, D.C.E. and A. G. MacIver. 1970. Endocarditis caused by a Coprinus species: A fungus of the toadstool group. J. Med. Microbiol. 4:370-374 18. Kern, M.E. and F.A. Uecker. 1986. Maxillary Sinus Infection Caused by the Homobasidiomycetous Fungus Schizophyllum commune. Journal of Clinical Microbiology. 23: 1001-1005. 19. Rippon, J. W. 1988. Medical Mycology: The Pathogenic Fungi and the Pathogenic Actinomycetes. W. B. Saunders Company Harcourt Brace Jovanovich, Inc. Philadelphia, PA, 797 p.