The dimorphic switch
Candida albicansis a dimorphic fungus. It normally
grows as a budding yeast, but in response to nutrient
limitation the yeast cells can produce a hyphal out-
growth (see Fig. 1.4). This dimorphic switch is central
to the pathogenicity of C. albicans, because invasion
of the mucosa is always achieved by hyphal growth.
In fact, this distinguishes C. albicansfrom all other (non-
pathogenic)Candidaspp. in clinical samples, and it is
used in a simple diagnostic test: the yeast is cultured
on a selective medium, then a loopful of inoculum is
transferred to a vial containing horse serum and incu-
bated at 37°C for 4 –5 hours. Of all the Candidastrains
that might occur in clinical samples only C. albicans
will sprout germ-tubes in these conditions, although
several other Candidaspp. from nonhuman sources
can do so. The hyphal stage is only transitory, and
incubation for longer times results in the production
of a pseudomyceliumin which the hyphae consist of
strings of sausage-shaped cells that produce budding
yeast cells at the septa (Fig. 16.4).
Progress in understanding the behavior of C. albicans
has been hampered by the fact that C. albicansis con-
stitutively diploid, so mutants are difficult to obtain.
Some homozygous recessive strains have been gener-
ated by repeated treatment with mutagens, especially
UV-irradiation. Also, parasexual genetics (Chapter 9)
has helped to generate mutants. For this, strains with
auxotrophic mutations are combined by protoplast
fusion, then allowed to regenerate walls. Some of the
resulting strains are tetraploid hybrids or aneuploids
which, when grown on minimal medium and subjected
to heat shock or antimicrotubule agents, can revert
to an altered diploid state by loss of chromosomes.
The development of molecular genetic methods for
C. albicanshas also been hampered. Many genes from
C. albicanscan be transformed into, and expressed
in, Saccharomyces cerevisiae, but not vice versa becauseC. albicanshas a nonstandard codon usage: the codon
CUG encodes serine, whereas it encodes leucine in
most other organisms. This is a significant limitation
because many of the putative virulence determinants
of C. albicanscannot be studied easily in the background
of the pathogen itself.The discovery of mating-type genesAs explained in Chapter 9, the mating system of the
ascomycetous yeast Saccharomyces cerevisiaeinvolves a
cassette of three mating-type genes (Mata 1 , Matα 1 and
Mat α 2 ) and the mating type of a strain can change,
depending on whether the MATa or MATα gene
is moved into the expression locus by a specific
transformation event. By contrast, nobody had ever
identified the equivalent mating-type genes of Candida
albicans, so this fungus had always been assumed
to be a clonal organism, with no capacity for sexual
recombination. However, in 1998 a single mating
type-like (MTL) locus was discovered in a laboratory
strain of C. albicans. Since there is only one MTL
locus, the cell must become homozygous for aor αby
mitotic recombination or gene conversion. An astrain
(a/a) cannot convert to α(α/α) because each strain has
lost the alternate MTLallele. This means that normal
strains of C. albicanscannot mate. But by deleting one
of the two MTLalleles it is possible to produce mating
strains that are either a/– or α/– and that, in appropriate
conditions, can fuse with one another. This was found
to be rare event, often leading to apparent tetraploids
that did not develop further. But a few a/– and α/–
strains were found to switch their phenotype from the
normal white colony appearance to an opaque colony
form, and these opaque strains have an increased
mating efficiency of about a million fold. Therefore, it
is proposed that C. albicanscan undergo mating but
does so only in the opaque colony form. The opaque
phase cells are stable ay 25°C but not at 37°C, and328 CHAPTER 16
Fig. 16.4(a,b) Pseudomycelium of Candida albicansin nutrient-limiting conditions. Yeast cells are produced instead of
fungal branches at the septa.(a) (b)FB4eC16 04/20/2005 02:53PM Page 328