Introduction to Fungi, Third Edition

ONYGENALES
291
Onygenaceae as human pathogens
The salient features of the four important
human pathogens are listed below. The points
at which C. immitis differs from the other three
are indicated.
1. All four species are probably mainly
saprotrophic in the soil, having become serious
pathogens mainly because of their ability to
grow at 37°C, evade the human immune system,
bind to human tissue, and produce proteases.
Pathogenicity is probably coincidental and
represents a dead end in the life cycle of these
fungi because the transmission of inoculum
from infected humans to the environment or
to other humans is negligible (Berbee, 2001).
Infection of humans occurs by inhalation of
microconidia produced in the soil. These are
sufficiently small to penetrate into the alveoli of
the lung. There, yeast-like stages are formed
which are the agents of disease. This is in contrast
to Candida albicans where hyphae rather
than yeast cells represent the invasive stage.
2. All species are dimorphic, with a
temperature-dependent switch from hyphae
(27°C) to yeast (37°C). In C. immitis, instead of
producing yeast cells at 37°C, the conidium
swells to produce an endospore-forming cyst or
spherule. In all four species, however, the switch
is relatively simple because the temperature shift
is sufficient to trigger it. This differs from C.
albicans in which the switch from yeast-like to
hyphal growth is influenced by a complexity of
environmental factors (see p. 277).
3. Pulmonary infections may take the form
of influenza-like symptoms in the majority of
immunocompetent patients but sometimes
develop into more severe tuberculosis-like
illnesses. Following initial infection, yeast cells
(or endospores) can be disseminated, causing
systemic mycoses in other organs. In the case of
mild infections, patients may make a complete
recovery and may then possess lifelong immunity.
This observation raises the possibility that
vaccines may be developed against these pathogens
(Cox & Magee, 2004; Nosanchuk, 2005) and
also against Candida albicans and other fungi
(Magliani et al., 2005).
4. The yeast cells of P. brasiliensis,
H. capsulatum and B. dermatitidis are internalized
by macrophages of their human hosts, but they
have a remarkable ability to survive and even
reproduce inside the lytic vacuoles by raising the
intravacuolar pH and withstanding the attack
of the lytic enzymes and the ‘oxidative burst’
created by the macrophages. Yeast cells inside
macrophages represent latent inoculum which
can cause relapses many years after the initial
infection, especially when the host’s immune
system becomes weakened by other causes. Thus,
these three species have been likened, in terms of
their pathology, to the bacterium Mycobacterium
tuberculosis (Borges-Walmsley et al., 2002; Woods,
2002).
5. Even prolonged chemotherapy may not
altogether eliminate the pathogens. The drugs in
common current use are similar to those applied
against C. albicans (p. 278) and include amphotericin
B and azole-type compounds (Harrison &
Levitz, 1996). Since long treatment periods are
required to control these diseases effectively,
the side effects of the drugs in current use are
problematic. The anti-Candida drug caspofungin
(see Fig. 10.9e) also shows promise against
onygenalean pathogens (Letscher-Bru &
Herbrecht, 2003).
6. Diseases caused by all four pathogens are
much more prevalent in men than in women,
often by a ratio of 10 : 1 or higher. This is due to
the inhibitory effects of oestrogen and other
female steroid hormones on the conidium yeast
transition (Hogan et al., 1996; Aristizabal et al.,
1998).
Ajellomyces capsulatus (anamorph Histoplasma
capsulatum)
Gymnothecia of this species (Fig. 11.3a) are easily
recognized, with a few conspicuous coiled
appendages and very small ascospores (