these represent two distinct species of Coccidioides
(immitisand posadasii), both of which cause the same
disease. Perhaps the most disturbing feature is that
Coccidioideshas the potential to be an inherently
virulent pathogen. It is known to have killed a healthy
laboratory technician, and the Occupational Safety
and Health Administration of the US Government
classifies it as “a biological agent with the potential to
pose a severe threat to public health and safety that
could potentially be used by terrorists.” Put in simple
terms, C. immitisis the only known fungus that is con-
sidered to represent a significant bioterrorism threat.
Further information on this fungus can be found at the
“Doctor Fungus” website (see Online resources).Histoplasma capsulatumHistoplasmais a fungus with a “typical” mould-yeast
dimorphism: it grows as hyphae on laboratory media
at 25–30°C, but as a budding yeast at 37°C on cysteine-
rich media. The hyphae produce single conidia on the
ends of short branches. Some of these conidia are
large, warty macroconidia(8–15μm) whereas others
are microconidia(2– 4μm) that are likely to be the
main infective agents in the lungs. The spores germi-
nate to form a germ-tube which rapidly gives rise to a
budding yeast phase in appropriate conditions. This
yeast phase is almost invariably found throughout the
course of infection, whereas the hyphae are involved
in the saprotrophic phase in dead body tissues or in
natural substrates.
Histoplasma capsulatumhas a wide geographical dis-
tribution, including much of the eastern USA, most of
Latin America, and parts of Southeast Asia, Africa and
Europe (e.g. Italy). It occurs naturally as a saprotroph
in fecal-enriched soil around poultry houses, in bat
droppings in caves, and also in starlings’ droppings
in towns and cities. The birds themselves are not
infected, and the fungus is not found in their fresh drop-
pings. However, bats have been found to be naturally
infected by H. capsulatum, with intestinal lesions.
Spores produced from fecal materials are the most
likely source of infection of humans, because there are
recorded instances of speliologists having developed the
disease (histoplasmosis) after visiting caves. Skin tests
using an antigen, histoplasmin, obtained from culture
filtrates suggest that a high proportion of the human
population has been exposed to infection in the
endemic areas; one such study estimated that 20% of
all the people in the USA had been infected at some
time from airborne spores.
Even in mild infections this fungus has been
detected in the urine, suggesting that it might com-
monly be generalized, although in the vast majority
of cases the infection resolves spontaneously. LikeCoccidioides, Histoplasmacan be acquired in the labor-
atory because there is a recorded instance of students
having tested positive after examining cultures in
the classroom. The airborne spores can readily enter
the lungs and cause acute pulmonary histoplasmosis.
However, chronic pulmonary infection is confined to
people with lung dysfunction from other causes, and
it can lead to dissemination to the other body tissues.
This dissemination occurs by carriage of the yeast cells
in the lymph system, and is most common in immuno-
deficient people or in the very young (less than 1 year)
or older (50 years or more) sectors of the population.
Magrini & Goldman (2001) describe the increasing
range of molecular genetic tools that have been used
to investigate the pathobiology of H. capsulatum.Blastomyces dermatitidisBlastomyces dermatitidis is an endemic dimorphic
fungus found in the southeastern and south central
regions of the USA, along the Mississippi and Ohio
rivers, where it causes a disease termed North
American blastomycosis, or Chicago disease. It is also
reported to be isolated from humans in parts of Africa
and the Indian subcontinent, but these strains lack
the characteristic antigens of B. dermatitidisand might
represent a different species. In North America infec-
tion is associated with moist soils enriched with organic
matter or rotting wood, but little is known about the
basic ecology of this fungus. When grown in laboratory
culture, it has narrow hyphae (about 2μm diameter)
that produce single globose conidia, 2–5μm diameter,
at the ends of short hyphal branches, similar to (but
smaller than) those of Thermomyces lanuginosus(see
Fig. 5.18). It infects humans from airborne conidia that
enter the lungs and transform into a thick-walled,
yeast-like budding phase. About 50% of infections
are asymptomatic, but other infections can progress to
an acute pulmonary phase after an incubation period
of 30 – 45 days, producing symptoms in the lungs that
strongly resemble a bacterial pneumonia. The infec-
tion can also progress to a chronic phase that affects
the lungs, skin, bones, genitourinary tract, and other
organs – for example, ulcerative lesions of the skin,
granulomatous inflammation of the lungs, and spread
to many other tissues and organs.
Brandhorst et al. (2002) reported that thermally
regulated dimorphism is the single most defining trait
of Blastomyces, and this is linked to a phase-specific gene
of B. dermatitidistermed BAD1(Blastomycesadhesin),
found only on the surface of the Y-phase and not on
the hyphae that grow at lower temperatures. The cell
wall glucan of the yeast-phase cells consists of 90%
α-glucan, whereas mycelial phase cells have roughly
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