FEMS Yeast Research, 16, 2016, fov116

doi: 10.1093/femsyr/fov116
Advance Access Publication Date: 21 January 2016
Editorial

Editorial: Candida glabrata, the other yeast pathogen

The ascomycete yeast Candida glabrata ranks second, in many specifically in pathogens. Finally, C. glabrata contains more

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studies, after Candida albicans as the most frequent yeast tandem repeats of genes than the other Nakaseomyces, at least
pathogen of humans, responsible for many types of opportunis- when examining the type strains (Gabaldon et al. 2013), and
tic infections, and most notable for the high mortality it pro- they mostly encode cell wall proteins, and, at least in the case
vokes in immuno-compromised patients. It was first described of the YPS tandem family, have been shown to be involved in
as Cryptococcus glabratus, isolated from human faeces in 1917 virulence (Kaur et al. 2007). It is likely that all Nakaseomyces are
(Anderson, 1917). Major breakthroughs in understanding the fortuitously pre-adapted to the human host, and commensality-
phylogeny and population structure of yeast and other fungal pathogenicity emerged independently in three species
pathogens, and indeed, many domains of the tree of life, were (Gabaldon et al. 2013).
brought about by recent progress in sequencing technologies. Although genus names are not to be trusted for phylogeny,
Since Saccharomyces cerevisiae opened the way by becoming the they do reveal interesting features. Nakaseomyces species used
first eukaryote to have its genome entirely sequenced, by an in- to be called “Kluyveromyces” and “Candida”. The name “Can-
ternational consortium (Goffeau et al. 1996), many full genomes dida” is given to ascomycetous yeasts that have no apparent
have been released, and yeast species account for a good num- sexual forms, i.e. no teleomorph. Remarkably, this name has
ber among eukaryotes, owing to the compactness and small size been mostly given to species which are pathogens of humans,
of their genomes. highlighting this common character of these pathogens, that
The genome of C. glabrata was published in 2004 (Dujon they seem to lose the ability to reproduce sexually, and seem
et al. 2004), as part of the Genolevures effort (http://gryc.inra.fr/). to be mostly “stuck” in a given ploidy. Availability of genome
Genomics confirmed previous gene analyses (Kurtzman and sequences was instrumental in kicking off new research into
Robnett, 1998), that showed that C. glabrata is much more closely sexual and parasexual cycles. Indeed, genomes reveal that they
phylogenetically related to S. cerevisiae than to C. albicans, de- contain homologs of all genes needed for mating, for meiosis,
scending from the same ancestor that underwent a whole sporulation and so forth. The iconic major yeast pathogen, the
genome duplication event. It remains one of the few pathogens diploid Candida albicans was long thought asexual, but examina-
from this branch of the phylogenetic tree of the Saccharomyc- tion of its gene content encouraged efforts to search for mating
etaceae. This is another demonstration of the fact that genus forms. This led to the discovery of a parasexual cycle (Hull et al.
names are not monophyletic in yeasts, and do not represent 2000; Magee and Magee, 2000). More recently, C. albicans has been
true lineages. Since then, two new pathogens have been de- shown to exist in the haploid phase (Hickman et al. 2013). It re-
scribed, Candida nivariensis (Alcoba-Florez et al. 2005) and Candida mains to be understood when and how the species goes through
bracarensis (Correia et al. 2006), that are part of the Nakaseomyces, these stages in its natural environment.
the clade described by C. Kurtzman to contain C. glabrata, Contrary to C. albicans, C. glabrata is isolated as haploid cells,
and up to that point, only three additional environmental and it has no described sexual cycle. As it is related to S. cere-
species, Nakaseomyces (Kluyveromyces) bacillisporus, Nakaseomyces visiae, the sexual cycle of this latter species must give us some
(Kluyveromyces) delphensis, Nakaseomyces (Candida) castellii, but clues as to what we should search for in C. glabrata. Some wild-
no other pathogen (Kurtzman, 2003). The genomes of the type S. cerevisiae isolates are homothallic (Katz-Ezov et al. 2010)
five known additional Nakaseomyces were published in 2013 which means that a single cell isolated after sporulation can give
(Gabaldon et al. 2013). This, in addition to the development of rise to diploid cells without having to encounter a cell of the op-
molecular tools, should allow easier experimental studies in all posite mating-type. This peculiar ability is shared by many fun-
Nakaseomyces; but at this point in time, obviously, most work has gal species, but mechanisms vary and it is most well-studied in
been performed on C. glabrata. S. cerevisiae. Homothallism in S. cerevisiae involves fusion of cells
Analysis of all Nakaseomyces genomes is reviewed in Angoul- of opposite mating-types, but haploid cells can undergo mating-
vant et al., and in Gabaldon and Carreté, this issue. All genomes type switching, which leads to mixed populations of cells, which
of the Nakaseomyces are small, especially those of the species can then mate to produce diploids. The underlying mechanisms
closely related to and including C. glabrata. All have lost most depend on the existence of a selfish gene, of the intein family,
gene copies resulting from the past Whole Genome Duplication that has been domesticated by S. cerevisiae. This gene encodes an
event, and genes involved in specific metabolic pathways. endonuclease, called Ho, that cuts the MAT locus, generating a
The one feature that distinguishes pathogenic species from dangerous double-strand break that is repaired by Homologous
non pathogens is the expansion of the EPA gene family, Recombination involving two additional loci, HMR (Hidden Mat

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Right) and HML (Hidden Mat Left), containing type a and type Finally, sequencing in addition to high-throughput
alpha information, respectively. genetical and biochemical tools in S. cerevisiae had led to
All Nakaseomyces genomes contain homologs of genes nec- an unprecedented level of understanding of this model yeast.
essary for mating-type switching, mating and meiosis (Fabre et It is essential that such methodology be applied on other
al. 2005; Muller et al. 2007; Gabaldon et al. 2013 and our unpub- species, and especially on pathogens, where comparisons to
lished results), although none of the Candida species are known a non-pathogenic model may be the least appropriate. Papers
to mate, or switch naturally (our own unpublished results). The by Roy and Thompson, and Usher et al., adress these issues,
HO gene from C. glabrata was over-expressed constitutively in with the comparative analysis of regulatory pathways and
the type strain, of MATalpha type, and MATa strains were ob- the development of synthetic lethal screens in C. glabrata.
tained (Edskes and Wickner 2013). Our results (Boisnard et al. All of these recent advances should help us understand the
2015) show that inducible expression of HO genes of various emergence of yeast pathogens related to baker’s yeast.
origins in C. glabrata can induce switching in both directions, This special issue (http://femsyr.oxfordjournals.org/content/
from MATalpha to MATa and back. We have also shown that ex- thematic-issue-candida-glabrata) is therefore an opportunity to
pression of mating-related genes seems less tightly regulated in put forward all progress which has been made recently thanks

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C. glabrata, so that several steps of the mating pathway may mostly to the genome sequences basis now available, and aims
not be functioning at optimal levels in experimental conditions to give an overview of future directions to explore.
(Muller et al. 2008). Nonetheless, it is likely that conditions for
mating will be found for the Candida species of the Nakaseomyces,
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