untitled

they are far more efficient in colonizing skin surfaces.

Therefore it is suggested that mating in this fungus must

occur outside the body – on the skin surface or in

environmental reservoirs.

Systemic infection by C. albicans

The rare cases of systemic spread of C. albicansin

the blood and lymph tissues are always associated

with severely predisposing factors such as leukemia,

advanced diabetes, prolonged corticosteroid therapy, etc.

But, strangely, C. albicansseldom grows systemically

in AIDS patients, who tend to develop other systemic

fungal infections instead. Candidagrows systemically

as a yeast in the body fluids, but dimorphism plays

an important role in one respect. If cells of C. albicans

are mixed with white blood cells (macrophages and

polymorphonuclear leucocytes) in vitrothe yeast cells

can be engulfed and destroyed, but some of them

break out of the phagocyes by converting to hyphae

and then produce a further population of yeasts. In these

conditions the vigor of the host defense system will

be crucial in containing an infection. In Chapter 17 we

will see that the major drugs used to treat systemic

candidosis (modern derivatives of ketoconazole and

related compounds) act synergistically with the host

defenses, because at even low concentrations they

suppress the transition from yeast to hyphal growth.

Opportunistic and incidental pathogens

Theoretically, any fungus that can grow at 37°C could

be a potential pathogen of humans, but in practice

the spectrum is much narrower than this (Table 16.1).

A few common saprotrophic species of Phialophora,

Sporothrix, Cladosporium, and Acremonium can infect

wounds and cause damaging subcutaneous mycoses.

Many examples of this are described by Kwon-Chung

& Bennett (1992). A different spectrum of fungi char-

acteristically infect through the lungs because their

airborne spores are small enough to reach the alveoli

(Chapter 10). Of all these fungi, the most significant

threat is posed by Aspergillusspecies, especially A.

fumigatusbut, to a lesser extent, A. flavus.We will focus

on these and related fungi in this section, because

Aspergillusinfections can be serious and often life-

threatening.

Aspergillosis

Aspergillus fumigatus, A. flavus and A. nigerare very

common saprotrophs on a range of organic materials

and produce abundant airborne conidia that are small

enough to enter the lungs (Chapter 10). In people

with impaired respiratory function these spores can

germinate to produce dense, localized saprotrophic

colonies termed aspergillomas (see Fig. 8.4). Usually

these remain noninvasive, surrounded by fibrous

tissue of the host. Aspergillomas are quite common

in poultry that are fed on moulded grain, and can occur

in farm workers who regularly handle such materials.

Infection of the lungs is entirely incidental so far as the

fungi are concerned because they grow as saprotrophs

on plant organic matter (Chapter 10) and they have

no natural means of disseminating from the lungs to

spread the infection to other hosts.

Aspergillus fumigatus is by far the most damaging air-

borne fungal pathogen of humans, and is responsible

for about 90% of aspergillosis cases. Its spores are

frequently inhaled and enter the lungs, but normally

are destroyed by the body’s innate defenses. However,

A. fumigatuscan become invasive and grow systemically

in the body, either from infections in the respiratory

tract of immunocompromised patients or after entry

through surgical wounds. It can be a potential prob-

lem in transplant surgery, when the patient’s immune

system is artificially suppressed.

There are thought to be two principal routes of

invasion by A. fumigatus– through the ciliated epithe-

lium that lines the upper regions of the respiratory

tract or through the alveoli. The cells of the ciliated

epithelium can engulf conidia of A. fumigatus, and some

of these engulfed spores can survive within the host

cells. Corticosteroid treatments are also known to be

a risk factor in invasive aspergillosis, by reducing

the release or efficacy of antifungal peptides produced

by the lining epithelium. The spores that are not

engulfed by the lining epithelium enter the alveoli,

where they can germinate, but are destroyed quite

rapidly by polymorphonuclear neutrophils. However,

low neutrophil numbers resulting from chemotherapy

can reduce the efficiency of this defense system.

The spores can also be engulfed quickly by alveolar

macrophages where they are killed by reactive oxygen

species. But the rate of killing is slow, and it can take

2–3 days to clear a respiratory challenge. These factors

can be important in determining the outcome of an

infection.

To date there is no evidence of a specific virulence

factor associated with A. fumigatus, and almost any strain

of this fungus seems to be able to infect compromised

individuals. The model system most commonly used

for this is inoculation of mice (the so-called murine,

i.e. mouse, model system). But this may not be the most

appropriate model for aspergillosis of humans. The

complete genome sequence of A. fumigatusis now

available (http://www.tigr.org/tdb/e2k1/afu1). This

should enable comparisons to be made of either

the transcriptome (messenger RNA) or the proteome

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