untitled

for Paracoccidioides brasiliensis(see below) and strains

of Histoplasma capsulatum– in all three cases the

reduced content of α-glucan correlates with loss of vir-

ulence in animal models. In B. dermatitidisthis corre-

lation between α-glucan and virulence was confirmed

by deleting the gene encoding BAD1. The deleted

strain had a diminished ability to bind to macrophages

or to mouse lung tissue, and it was highly attenuated

in experimental mice. Restoration of the BAD1gene by

transformation restored the virulence of B. dermatitidis

and restored the adhesive properties of the fungus. The

BAD1 protein has been found to self-associate in the

presence of calcium ions, and it is suggested that, in

the conditions of the lung, chitin-bound BAD1 mole-

cules could begin to capture further BAD1 molecules,

adding further α-glucan layers to the yeast cell wall.

Paracoccidioides brasiliensis

Paracoccidioides brasiliensisis another endemic fungus,

found mainly in subtropical forest regions of Central

and South America, especially Brazil, Venezuela, and

Columbia. It has been isolated from the digestive tract

of some animals (e.g. armadillos; Silva-Vergara et al.

2000) and from moist soil enriched with proteins, but

the natural ecology of the fungus is poorly understood.

It is a mitosporic fungus with no known sexual stage,

and it grows very slowly in agar culture. P. brasiliensis

is a dimorphic fungus that grows as mycelia at lower

temperatures but as a budding yeast at 37°C or in

body tissues. The yeast cells are oval or spherical and

range in size from 2 to 10μm or up to 30μm or more.

Often, they grow as a single large central cell with

multiple buds attached to the central cell by narrow

necks, resembling a mariner’s wheel. The buds remain

attached to the mother cell until they, themselves, bud

(Fig. 16.7).

P. brasiliensiscauses the disease termed paracoccid-

ioidomycosis, or South American blastomycosis.

Infection is assumed to occur from airborne spores

that enter the lungs, but most infections are asymp-

tomatic, as evidenced by a skin test to the fungal anti-

gen. In other cases the infection can develop several

years after initial exposure, indicating a long latent

period in which the fungus has remained dormant

in the lymph nodes. Such infections are probably

associated with immunodeficiency. The characteristic

form of the disease involves severe ulcerative lesions

of the mouth, nose, larynx, and subcutaneous tissues,

causing serious facial disfigurement. In extreme cases

the fungus can also affect other organs such as the

spleen, liver, bones, and central nervous system. A

notable feature of paracoccidioidomycosis is that it

occurs primarily in men – the ratio of infection is about

15 : 1 in men compared with women, but can be up

to 78 : 1, whereas equal numbers of men and women

show a positive skin test reaction to the paracoccidioides

antigen. The reason is that estrogens inhibit the trans-

ition of cells from the conidial or mycelial form to the

yeast phase which is necessary for colonization of the

tissues (Borges-Walmsley et al. 2002).

Cryptococcus neoformans

Cryptococcus neoformansdiffers from the fungi dis-

cussed above because it is not endemic but has a wide

global distribution. It is common as a saprotroph

and has been isolated frequently from old, weathered

pigeon droppings in cities and from soils enriched

with bird excreta. However, it does not compete well

in wet droppings, where bacteria can raise the pH to

growth-inhibitory levels, and it does not infect the birds

themselves. Studies in New York City indicate that a

high proportion of young children have been exposed

to the fungus, because they show a reaction when skin-

tested with the Cryptococcus antigen, but apparently

do not develop any symptoms. There are over 30 spe-

cies of the yeast Cryptococcus, but only one species,

C. neoformans, is pathogenic to humans, causing the

disease called cryptococcosis.

Cryptococcosis used to be a rare disease, found

mainly in people who were naturally immuno-

compromised or who had undergone transplant

surgery involving immunosuppressive drugs. But the

THE MOULDS OF MAN 333

Fig. 16.7Typical appearance of the budding phase of

Paracoccidioides brasiliensis: the large parent yeast-like

cell produces multiple buds that remain attached to the

mother cell.

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