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Fungi cause diseases in all sorts of animals,
including humans, insects, and even microscopic nematode worms.
Here, we shall focus on some key diseases of humans and other mammals.
1.
Dermatophytes
2.
Aspergillus
3.
Cryptococcosis
4.
Coccoidomycosis
5.
Histoplasmosis
6.
Candidiasis
7.
Pneumocystis carinii Pneumonia (PcP)
1. Dermatophytes
The dermatophytes, as the name
suggests, like skin. These fungi are ascomycetes
which cause infection on or just under the skin. There are some
forty fungal species which cause skin infections in mammals, but
perhaps the most important are the Trichophyton fungi which
cause such infections as ringworm and athlete’s foot. These
fungi are biotrophic in the sense that they tend
not to kill their hosts. In humans, the major areas where dermatophytes
lurk are in flakes of skin and hair left in changing rooms, leisure
centres, on shared clothes and towels, in fact, anything that is
dry enough not to allow good bacterial growth and is shared between
at least two different humans. The diseases caused by dermatophytes
are discomforting and unsightly, but uncomplicated infection is
rarely fatal.
2. Aspergillus
Most Aspergillus species are harmless;
however, three species, A. niger, A. flavus and
A. fumigatus produce large numbers of conidia
which can cause infection (aspergillosis). The
infection occurs if the conidia establish themselves in human lungs,
forming dense colonies of growth called aspergilloma
which can impede breathing.
Aspergillus species are a good model of
how fungi cause disease, for it has three modes of causing illness:
| i. |
Farmer’s lung.
This is an allergic disease caused by exposure to spores of
the fungus. It is called farmer’s lung as A. fumigatus
grows well on mouldy hay, as well as other stored crops. When
a person is sensitized to antigens on the spore, they will
suffer breathing difficulties due to pneumonitis, an inflammation
of the lungs. |
| ii. |
Mycosis. This is extremely serious, but it
is usually limited to immunocompromised
individuals with weakened immune systems. Aspergillus
spreads systematically and invasively throughout the body causing
severe illness. |
| iii. |
Aflatoxin. This toxin,
produced by two Aspergillus species, including A.
flavus (hence Aflatoxin), has
the strong potential to cause cancer, and it can suppress the
immune system. Aflatoxin is a peptide
toxin, with thirteen types, the most harmful being Aflatoxin
B1. These can be identified using a method called Thin-Layer-Chromatography
which separates them on
the basis of their size and constitution. Aflatoxin
has been the subject of development as a biological weapon,
but in nature, the main hazard is the ingestion of Aflatoxin
on food crops such as grain or peanuts or its inhalation in
dust from crops. |
Lest we think that all Aspergillus fungi
are bad, it’s perhaps worth remembering that Aspergillus
is used in biotechnology
to produce citric acid,
which acts to stop soft drinks and other foods from getting too
acid.
3. Cryptococcosis
The agent responsible for this disease, Cryptococcus
neoformans (or Filobasidiella neoformans) is a haploid
dimorphic yeast
in the phylum Basidiomycota
and causes a flu-like illness in healthy adults. In immunocompromised
people, though, it has the potential to cause extremely serious
infections. It is currently the fourth most common life threatening
disease of AIDS patients in the USA. In such patients, after the
initial flu-like illness, complications may occur, and the yeast
can spread to the central nervous system (CNS). Once in the CNS
it tends to grow extremely well in the cerebral cortex, brain stem
and the meninges (where it causes meningitis, or
inflammation of the meninges). Unless treated, C. neoformans
infections of the CNS are always fatal.
People may acquire C. neoformans from an
aerosol or fine spray of the yeast arising from
dried bird droppings. Once inhaled into the lungs, it can cause
the mild flu-like illness, and subsequently lie dormant for years,
until the host’s immune system is weakened and it can spread
to the CNS.
Cryptococcus is an unusual fungus, and
the clue to this is in the name, which when translated from Latin
means hidden sphere. This is apt, as the yeast is spherical,
and insulated from the outside world by a polysaccharide capsule.
This capsule is important in allowing the fungus to escape the attentions
of the host’s immune system.
4. Coccoidomycosis
The agent of this disease is a dimorphic
yeast, Coccoides
immitis, limited to semi-arid and arid areas of the Americas
that is highly resistant to alkaline pH and temperatures up to 40oC.
Within endemic areas, up to half of the local human
population may show serological (antibodies) evidence
of infection, but severe infection is rare: in most cases, people
only ever find out they’ve had coccoidomycosis when they are
tested for antibodies to it. The fungal spores are highly infectious,
and they are frequently carried on the wind in dust storms.
People unfortunate enough to develop the severe
form of the disease usually develop pneumonia,
which may spread to other tissues, and cause damage to bones, connective
tissue and major organs. Meningitis may occur.
Apart from medical microbiologists who accidentally expose themselves
to large amounts of the highly infectious spores, most cases of
the severe form are found in immunocompromised
people. Like Cryptococcus, the disseminated form of the
disease is extremely serious, and fatalities aren’t infrequent.
Apart from humans, many other mammals are susceptible
to C. immitis including bottle-nosed dolphins in warm,
tropical waters.
5. Histoplasmosis
Histoplasma capsulatum causes an extremely
common but rarely noticed disease called Histoplasmosis. One epidemiological
study suggests that about 20 % of Americans have at one time been
infected with spores of the fungus. H. capsulatum is a
dimorphic yeast
which reproduces by means of conidia.
This ascomycete
is common in bird and bat droppings, but evidence of infection in
birds is rare. H. capsulatum can cause acute lung pathology
in people with weakened immune systems, but given the aggressive
nature of Histoplasma, even otherwise healthy people can
be severely affected.
6 . Candidiasis
Dimorphic
yeasts in the family
Candida, particularly Candida albicans are organisms
which live on our skin, our mucous membranes, and our lower digestive
tract, rarely bothering us. However, if Candida proliferates,
it can cause irritation, and in extreme cases death.
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The condition caused is termed Candidiasis
and is commonly known as “thrush” due to the white,
speckled appearance of the mycosis. Key factors in the proliferation
of Candida include abrasion of the skin or mucosa,
high levels of the hormone progesterone and stress. The severity
of the condition depends also on the strength of binding between
the Candida cells and the human cells.
An important factor also is the dimorphism
of Candida which allows the yeast to grow in the
hyphal form, allowing effective colonisation of the mucosal
surfaces and skin. |
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7. Pneumocystis carinii
Pneumonia (PcP)
Pneumocystis carinii (or Pneumocystis
jiroveci) is a yeast which causes invasive pneumonia in AIDS
patients. Not much is known about the biology of P. carinii
/ jiroveci – until recently it was thought it was a protozoan.
Pneumocystis carinii is exceedingly common and rarely causes
noticeable disease in healthy humans. However, in immunocompromised
patients, PcP occurs and often spreads to other organ systems of
the body. In immunocompromised patients infected with PcP, Trimethroprim
- sulfamethoxazole is currently the treatment of choice.
| You
may be starting to notice a trend in the nature of fungal
pathogens of animals. They tend to be dimorphic
yeasts that are common in nature, but rarely cause
noticeable disease. When such fungi do cause disease, however,
the disease is severe and invasive to the extreme, and occurs
most frequently in immunocompromised
patients, such as recent transplant recipients, HIV-AIDS patients,
the very old and the very young, cancer patients and victims
of major trauma.
Dimorphism
is often mediated by a change in nutrient levels, temperature
or humidity. Recall that in baker’s yeast, Saccharomyces,
the spherical yeast form gives it an advantage when growing
in liquid media. The same concept can be applied to human
pathogens. Hyphal forms, by contrast, are better suited to
growth and spread outside the body.
Such invasive
growth is hard to deal with. If one were to make a
list of the salient points of the cell and molecular biology
of fungi and compare them to the salient points of human cell
and molecular biology, then there would be few differences
(eukaryotic, membrane enclosed organelles, similar metabolic
pathways …). As a result, the development of antifungal
drugs that will kill or control the fungi, but will not have
side-effects on the human patient, is difficult.
Taking into consideration the
global epidemic of HIV and the improvements in supportive
care made possible by medical technology, it can be seen the
niche for such pathogens is expanding at a worrying rate. |
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