Introduction to Fungi, Third Edition

662 BASIDIOMYCETE YEASTS
in that its basidiospores are rod-shaped rather
than spherical or ellipsoid.
As with most if not all fungi pathogenic to
man, the ability of C. neoformans to cause disease
is serendipitous, and the human body represents
a dead-end in the life cycle of the pathogen.
Disease outbreaks are preceded by contact of
humans with the fungus in its natural habitat,
but the precise identity of this has been difficult
to track down. Ellis and Pfeiffer (1990a) noted the
geographic co-occurrence of human cases caused
by C. neoformans var. gattii and the distribution of
Eucalyptus camaldulensis trees in Australia, and
were able to show that the fungus is associated
with the flowers, bark and litter of Eucalyptus.
In other countries, different plants may also
act as hosts. Further, clinical and environmental
isolates of C. neoformans var. gattii in Australia
have been shown to be genetically identical
(Sorrell et al., 1996). Thirdly, the confinement of
C. neoformans var. gattii to rural areas may explain
why its abundance has barely increased in the
wake of the AIDS epidemic, in marked contrast
to var. neoformans and especially var. grubii which
accounts for 99% of infections in AIDS patients
(Mitchell & Perfect, 1995). Both these latter
varieties are common in urban habitats, being
associated with the nests and droppings of birds,
especially pigeons (Emmons, 1955) but also caged
birds. Although birds certainly spread the
fungus, they are more likely to be vectors than
primary hosts in nature because they are not
themselves affected by cryptococcosis. As yet
unidentified plants are probably the primary
substratum, and Lazéra et al. (1996) have shown
that C. neoformans var. neoformans (presumably
including var. grubii) occurs in the hollows of
living tree trunks.
Whereas C. neoformans var. gattii, like
Eucalyptus camaldulensis, is confined to tropical
and subtropical areas, vars. neoformans and grubii
are cosmopolitan.
Life cycle
The life cycle of F. neoformans is unusual in
several respects (Kwon-Chung, 1998) as shown in
Fig. 24.2. The fungus is heterothallic with a bipolar
mating system (two mating types, a and a).
The yeast cells are haploid and uninucleate,
and they reproduce by budding. Conjugation
between two cells of compatible mating types
gives rise to a limited dikaryotic mycelium with
septa bearing clamp connections. From this,
elongated metabasidia arise and terminate in a
swollen tip. Nuclear fusion occurs in the basidial
stalk, and meiosis followed by repeated mitotic
divisions in the swollen apex. This produces four
patches which bud off a chain of basidiospores,
each of which contains a single haploid nucleus.
Meanwhile, mitosis continues in the basidial
cytoplasm. Each patch can produce numerous
basidiospores so that a column consisting of four
chains is formed. The migration of nuclei into
the basidiospores is random so that each chain
may contain basidiospores of both mating types.
This kind of basidium is unique to F. neoformans.
‘Self-fertility’ is a frequently observed
phenomenon in a mating type strains of
F. neoformans and involves the production of a
monokaryotic mycelium with incomplete clamp
connections, giving rise to basidia and basidiospores
presumably without meiosis (Wickes et al.,
1996). These should therefore be called conidia.
Of all varieties of C. neoformans, strains containing
mating type a are isolated much more
frequently than a strains from natural situations
as well as from patients (Kwon-Chung & Bennett,
1978), and the ability of a but not a strains to
form dry wind-dispersed conidia may explain
their greater abundance in nature. Kwon-Chung
et al. (1992), working on strains of C. neoformans
var. neoformans which were genetically identical
to each other except for their mating type, found
that the a strain was also more virulent than the
a strain. The conclusion was that the a idiomorph
might encode virulence factors.
Both a and a mating type idiomorphs of
C. neoformans var. neoformans and var. grubii have
now been sequenced (Lengeler et al., 2002) and
were found to be unusually large (105 130 kb).
Approximately 20 genes are encoded by the
entire sequence, including pheromones, receptors,
transcription factors and components of
signalling cascades. Several genes are unique to
either a or a, and even those common to both are
arranged in different positions, making recombination
within the mating type region impossible.
Lengeler et al. (2002) have likened the