Uneven Distribution of Mating Types among Genotypes of Candida glabrata Isolates from Clinical Samples

Abstract

In order to shed light on its basic biology, we initiated a population genetic analysis of Candida glabrata, an emerging pathogenic yeast with no sexual stage yet recognized. A worldwide collection of clinical strains was subjected to analysis using variable number of tandem repeats (VNTR) at nine loci. The clustering of strains obtained with this method was congruent with that obtained using sequence polymorphism of the NMT1 gene, a locus previously proposed for lineage assignment. Linkage disequilibrium supported the hypothesis of a mainly clonal reproduction. No heterozygous diploid genotype was found. Minimum-spanning tree analysis of VNTR data revealed clonal expansions and associated genotypic diversification. Mating type analysis revealed that 80% of the strains examined are MATa and 20% MAT␣ and that the two alleles are not evenly distributed. The MATa genotype dominated within large clonal groups that contained only one or a few MAT␣ types. In contrast, two groups were dominated by MAT␣ strains. Our data are consistent with rare independent mating type switching events occurring preferentially from type a to ␣, although the alternative possibility of selection favoring type a isolates cannot be excluded.

Evaluation of Polymorphic Locus Sequence Typing for Candida glabrata Epidemiology

“…CgMT-J and CgMT-M yielded largely congruent results despite representing distinct chromosomes and coding versus noncoding loci. This congruence indicates that these single loci provide reliable phylogenetic information, and it confirms that C. glabrata is a predominantly clonal species in which sexual reproduction and horizontal gene transfer have contributed minimally to its evolution (30,33,43). On the other hand, this clonality means that strain resolution can be limiting; this is illustrated by large clusters such as N that include geographically diverse isolates (3 countries and at least 5 U.S. states).…”

“…The most widely applied include (i) multilocus sequence typing (MLST), which analyzes 6 relatively conserved housekeeping loci for single nucleotide polymorphisms (SNPs) (29,30), (ii) pulsed-field gel electrophoresis (PFGE), which compares total DNA banding patterns with or without restriction enzyme digestion (14,23,31), (iii) multilocus variable-number tandem-repeat analysis (MLVA, also known as microsatellite analysis), which examines length variation in 6 to 9 PCR-amplified loci that contain polymorphic tandem repeats (32)(33)(34)(35), and (iv) random amplification of polymorphic DNA (RAPD), which compares banding patterns following PCR with a nonspecific primer (26,36). In general, these methods are comparable in their strain resolution, achieving diversity indexes of ca.…”

Discovery of a phenotypic switch regulating sexual mating in the opportunistic fungal pathogen Candida tropicalis

“…Homologs of Wor1 are found across the entire fungal lineage (24), although the white-opaque switch is thought to be unique to C. albicans (and its sister species C. dubliniensis), and has not been described in any other hemiascomycete species (25)(26)(27). In contrast to C. albicans, sexual mating has never been observed in C. tropicalis, C. parapsilosis, or C. glabrata, despite extensive efforts to find laboratory conditions conducive to mating (28)(29)(30)(31)(32). Sequence analysis reveals that "asexual" Candida species contain MAT/MTL loci resembling those of sexual species, and they encode many of the genes necessary for mating and meiosis (10,11,31).…”

Multilocus Microsatellite Markers for Molecular Typing of Candida glabrata : Application to Analysis of Genetic Relationships between Bloodstream and Digestive System Isolates

“…A microsatellite-based typing method using a new set of eight markers has been set up for population genetic analysis of C. glabrata (14). In this work, we positively evaluate this method, which has a discriminatory power calculated at 0.97, for tracing C. glabrata strains.…”