increasing incidence of HIV/AIDS in the 1980s and
1990s led to a major surge in cryptococcosis, affect-
ing 7–10% of AIDS patients worldwide. Although the
disease can be treated with routine administration of
antifungal agents, this is seldom possible in develop-
ing countries. The typical route of infection is via the
lungs, when spores or yeast cells are inhaled. After an
initial subclinical pulmonary infection, the fungus
can cause chronic lung infection and then disseminate
to the central nervous system, where it shows a pre-
dilection for growth in the cerebral cortex, brain stem,
cerebellum, and meninges. This is invariably fatal if not
treated, and it is common in AIDS patients, perhaps
because a primary lesion in the lung has remained qui-
escent for many years and leads to secondary spread
when the immune system is impaired.
There are several features of C. neoformans that have
yet to be resolved and that could assist in preventing
or treating infections. Normally the fungus is isolated
from environmental samples as a haploid yeast, and
it was commonly assumed that dehydrated yeast cells
are the primary source of infection. With a diameter
ranging from 2.5 to 10μm, some of these cells would
be small enough to reach the alveoli, rehydrate, and
initiate infection. However, more recently it was
discovered that C. neoformanshas a sexual stage in
the genus Filobasidiella (Basidiomycota; Fig. 16.8),leading to the production of airborne basidiospores
about 1.8–3.0μm diameter. These would be an ideal
size to be deposited in the alveoli (Chapter 10). The
basidiospores can be produced in laboratory culture
by pairing of the two mating types, termed “a” and
“α”. But αstrains alone can be induced to produce
basidiospores (with a single haploid nucleus in each
cell) when cultured on media that lack nitrogen
and in conditions of water-stress. The αmating-type
locus (MATα) has been cloned and shown to encode
a pheromone-like peptide. The αstrains are found
much more frequently than are the a mating types in
clinical specimens, and in inoculations of mice they
cause much more rapid death than do the a-mating-
type strains. Thus it seems that the gene product of
α-mating-type strains may contribute to virulence.
In addition to these points, there are two distinct
forms of C. neoformans, classified as varieties – C.
neoformans var. neoformans and C. neoformans var.
gattii. The first of these is commonly associated with
AIDS infection in Europe and North America, and pre-
sumably originates from bird excreta. By contrast, the
variety gattiiis seldom found in AIDS patients; instead
it is associated with endemic disease of nonimmuno-
compromised people in Australia, Papua New Guinea,
and parts of Africa, India, south-east Asia and Central
and South America. The environmental source of334 CHAPTER 16
Fig. 16.8Cryptococcus neoformansand its sexual stage, Filobasidiella neoformans. The budding yeast cells (Y-phase) of
opposite mating types conjugate and form a dikaryotic cell. This forms a mycelium on which the inflated basidia develop.
Meiosis in the basidia leads to the production of four haploid nuclei, which migrate to the tips of the basidia. Then
chains of four haploid basidiospores are produced, and these germinate to give the haploid Y-phase cells.FB4eC16 04/20/2005 02:53PM Page 334