Introduction to Fungi, Third Edition

CANDIDA (ANAMORPHIC SACCHAROMYCETALES)
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but are usually displaced by S. cerevisiae later.
Candida albicans is slightly atypical of the genus
in that it does not appear to be distributed
widely in the environment and can be considered
a commensal of humans and other warmblooded
animals.
10.3.1 Dimorphism in Candida albicans
Candida albicans can grow as yeast cells, true
septate hyphae, or pseudohyphae which are an
intermediate form between these two extremes
(see Fig. 1.1d). Thick-walled chlamydospores
may be formed by hyphae or pseudohyphae.
This dimorphism or polymorphism has long
been thought to represent an important pathogenicity
determinant, pathogenicity commonly
being associated with hyphal growth whereas
yeasts are indicative of saprotrophic commensal
growth. The switch between yeast and hyphal
states is reversible and is determined by an interplay
of several factors, e.g. temperature (hyphae
at 37°C, yeasts below), pH (hyphae at neutral
pH, yeasts at acid pH), nutrient abundance
(yeast growth) or deficiency (hyphal growth),
and presence (hyphal growth) or absence
(yeast growth) of blood serum. Thus, conditions
which mimic the bloodstream encourage hyphal
growth, whereas conditions as found on the skin
or in mucosal linings tend to promote yeast
growth. Candida albicans is a commensal colonist
of most humans, occasionally causing skin
lesions, but under exceptional circumstances it
turns into a serious pathogen causing deepseated
or systemic mycoses, especially when the
host’s immune system is weakened, e.g. in
AIDS sufferers or patients who have undergone
an organ transplantation. From such infections,
C. albicans is usually recovered in the
hyphal form.
The yeast and hyphal forms differ in many
features which have a bearing on their ability
to cause disease (Odds, 1994). For instance,
hyphae are coated with mannoproteins which
adhere strongly to mammalian proteins found
in the membranes of cell surfaces. Such adhesive
proteins (adhesins) take the shape of fimbriae
projecting beyond the cell wall (Yu et al., 1994;
Vitkov et al., 2002; see Fig 23.15). Enhanced
adhesion may play a role in pathogenesis,
especially when coupled with the invasive
mode of growth displayed by hyphae (Gow
et al., 1999). Further, hyphae secrete aspartyl proteases
and lipases capable of degrading host
tissue (Hube & Naglik, 2001). Mannoproteins as
well as proteases are potential targets for new
anti-Candida drugs.
Yeast-hyphal dimorphism in C. albicans has
been investigated in some detail. The signalling
chains leading to the formation of a hypha are
extremely complex, involving cyclic AMP as well
as mitogen-activated protein kinase (MAP kinase)
pathways. Both are also involved in the switch
from yeast cells to pseudohyphal growth in
S. cerevisiae (Brown & Gow, 2002). An extensive
cross-talk between different signalling pathways
is not surprising, since the switch from yeast to
hypha responds to many different environmental
signals which need to be integrated. The
control mechanisms determining the switch
from yeast to (pseudo)hyphal growth may also
be similar between S. cerevisiae (see Section 10.2.4)
and C. albicans.
10.3.2 Mating and switching in
Candida albicans
Whereas C. albicans is permanently diploid, other
Candida species such as C. glabrata are haploid.
An exclusively diploid vegetative phase is very
unusual among true fungi, although it is found
in Protomyces (Archiascomycetes; see p. 251)
or Xanthophyllomyces (Heterobasidiomycetes; see
Fig. 24.3) and, of course, in the Oomycota
(see Chapter 5). Until recently, C. albicans was
thought to reproduce strictly asexually. However,
when the genome sequence of C. albicans became
available and was examined closely, a complete
set of genes relevant to mating, homologous
with those known for S. cerevisiae, was detected,
and it was found that the fungus is heterozygous
for the two mating type idiomorphs a and
a, similar to the diploid cells of S. cerevisiae but
unable to sporulate. The signalling processes
involved in mating are likely to be similar
between S. cerevisiae and C. albicans (Bennett &
Johnson, 2005), and conjugation in C. albicans has
now been observed between diploid strains each