untitled

(protein profile) of strains grown in vitrocompared with

in vivo, to identify any potential virulence determinants

that are expressed specifically in the host environ-

ment. Details of the roles of Aspergillusspp. as human

pathogens are covered by several contributors in

Domer & Kobayashi (2004).

Endemic dimorphic fungi

In addition to C. albicans, a small group of fungi can

cause systemic infections of healthy or immunocom-

promised individuals. These fungi are particularly

interesting because they are geographically localized

(endemic) and they are dimorphic, switching from one

growth form to another in response to temperature

shifts. All of them initiate infection from airborne

spores that enter the lungs. People with impaired

respiratory function can be particularly prone to lung

infection, and people in the advanced stages of diabetes,

leukemia, and immunosuppressive disorders can often

develop the systemic disease. Yet, skin tests with anti-

gens of some of these fungi indicate that a substantial

proportion of the population in the endemic areas has

been exposed to infection at some stage and perhaps

suffered only mild, flu-like symptoms before the infec-

tion spontaneously resolved. Thus, these fungi pose

a significant and perpetual threat to a sector of the

population. The four main pathogens that cause these

diseases are discussed below.

Coccidioides immitis

Coccidioides immitisand a related species, C. posadasii,

are fungi that grow in the alkaline soils of arid desert

regions of California, Arizona, and Texas, extending

into parts of Central and South America. The hyphae

of these fungi fragment to produce small, thick-walled

spores (arthroconidia or arthrospores) which can be dis-

persed in dry, wind-blown dust and thereby enter the

lungs. Most of these cells are engulfed and destroyed

by macrophages in the lungs, and cause a flu-like

or pneumonia-like infection which resolves spontane-

ously. The incidence of this is quite common among

people who live in these desert areas, because up to 50%

of healthy people show a positive response to a skin

test with Coccidioidesantigen, obtained from laboratory

cultures of the fungus.

However, in some people – especially those who

are immunocompromised – the fungus is not con-

tained by macrophages and it can spread within the

lungs and enter the bloodstream, causing a serious gen-

eralized infection of the bones, subcutaneous tissues,

meninges, and major organs. This disease is called

coccidioidomycosis.

As shown in Figs 16.5 and 16.6, in the aggressive,

generalized phase of coccidiodomycosis, the arthro-

conidia swell and undergo multiple nuclear divisions,

leading to the production of multinucleate, swollen

structures termed spherulesin the lungs. The large

330 CHAPTER 16

Fig. 16.5Infection cycle of Coccidioides immitis, which grows in desert soils. In its saprotrophic phase, the fungus pro-

duces hyphal branches that undergo multiple septation to form a chain of cells. Then the nutrients are withdrawn from

every alternate cell, to supply nutrients for the remaining cells (arthrospores) which develop thick walls. Arthrospores

carried in wind-blown soil enter the lungs, germinate and produce a multinucleate spherule. At maturity, the cytoplasm

cleaves around the individual nuclei, and the spherule releases uninucleate cells that can develop into further spherules.

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