Introduction to Fungi, Third Edition

278 HEMIASCOMYCETES
Fig10.8 Examples of
white opaque switching in
Candida albicans.(a)Cellsfroma
white colony plated at low density.
A switch has occurred from white
(wh) to opaque (op). (b) A white
colony which has been aged on a
plate with limited gas exchange.
This has caused increased rates of
switching from white (wh) to
opaque (op) at the colony edge.
Original images kindly provided by
D.R. Soll and K. Daniels.
containing only either mating type, although
karyogamy was doubtful and meiosis was not
observed (Magee & Magee, 2000; Lockhart et al.,
2003). If tetraploid strains result from karyogamy
in nature, these may undergo meiosis or random
loss of chromosomes by a parasexual cycle,
i.e. C. albicans may have a cryptic sexual phase
in its life cycle which has eluded mycologists
for over a century (Gow, 2002). Wong et al. (2003)
have suggested that Candida glabrata has a
similarly cryptic sexual cycle.
In contrast to S. cerevisiae, there are no silent
additional copies of mating type idiomorphs
in the genome of C. albicans. Before a diploid
strain of C. albicans heterozygous for mating
type idiomorph (i.e. a/a) can mate, it will therefore
have to convert to a/a or a/a by a mechanism
different from the mating type switch based
on a cassette system as found in S. cerevisiae
(see p. 266).
A remarkable phenomenon that has been
known for some time is the spontaneous and
reversible switching of yeast colony phenotypes
in C. albicans. A given strain can switch its colony
morphology between smooth, wrinkled or starlike,
and white or opaque (Fig. 10.8). The
latter switch is particularly well-characterized
(Slutsky et al., 1987; Soll, 2002) and occurs at
an unusually high frequency (about one colony
in 1000 10 000). The different morphological
appearances of white and opaque colonies are
due to differences in size, shape and surface
properties of the yeast cells. Genetically, the
switch is accompanied by the co-ordinated upor
down-regulation of numerous genes, some of
them potentially involved in pathogenesis
(Soll, 2003). Examples are secretory proteases
or an ABC transporter involved in drug resistance
(see p. 278). Not surprisingly, these two
different colony types have widely differing
pathogenic properties, the white-phase cells
appearing to be better adapted to colonization
of internal organs and opaque-phase cells superior
in colonizing external skin regions.
An interesting link between mating and
switching is that the latter is suppressed in
strains heterozygous for the mating type idiomorphs
a and a. This may be mediated by the
regulatory heterodimer presumably formed by
protein products of the a and a idiomorphs.
Another noteworthy observation involves sexual
reproduction: opaque cells mate about 10 6
times more efficiently than white cells (Miller &
Johnson, 2002). Mating competence in C. albicans
is therefore regulated at two levels, namely the
requirement for a given cell to be homozygous
for mating type (either a or a) and to be in the
opaque state (Soll et al., 2003). It is furthermore
possible that some of the phenotypes characteristic
of opaque cells are required for mating, in
addition to or instead of being pathogenicity
factors. In this context, it is of interest that
there is a mass switch from opaque to white
at 37°C, and that mating between opaque cells
of opposite mating type is strongly stimulated
on skin surfaces which have a lower temperature
(Lachke et al., 2003). Clearly, the ability of
C. albicans to adapt to different situations by
changing between several pre-programmed cell
types, e.g. the mating-competent opaque and the
invasive white cells, contributes to the success