Genomes shed light on the secret life of Candida glabrata: not so asexual, not so commensal

Abstract

Candida glabrata is an opportunistic yeast pathogen, whose incidence has increased over the last decades. Despite its genus name, this species is actually more closely related to the budding yeast Saccharomyces cerevisiae than to other Candida pathogens, such as Candida albicans. Hence, C. glabrata and C. albicans must have acquired the ability to infect humans independently, which is reflected in the use of different mechanism for virulence, and survival in the host. Yet, research on C. glabrata suffers from assumptions carried over from the more studied C. albicans. Regarding the adaptation of C. glabrata to the human host, the prejudice was that, just as C. albicans, C. glabrata is a natural human commensal that turns deadly when immune defenses weaken. It was also considered asexual, as no one has observed mating, diploids, or spores, despite great efforts. However, the recent analysis of whole genomes from globally distributed C. glabrata isolates have shaken these assumptions. C. glabrata seems to be only secondarily associated to humans, as indicated by a lack of co-evolution with its host, and genomic footprints of recombination shows compelling evidence that this yeast is able to have sex. Here, we discuss the implications of this and other recent findings and highlight the new questions opened by this change in paradigm.

The role of Lactobacillus species in the control of Candida via biotrophic interactions

“…Similar to S. cerevisiae, C. glabrata grows only in yeast form. Detailed genomic analyses show the divergence of the C. glabrata isolates into several distinguishable clades and document remnants of occasional mating events [78][79][80]. Other human pathogenic Candida species like C. tropicalis or C. dubliniensis are closer related to C. albicans [81].…”

Pathogenic Budding Yeasts Isolated outside of Clinical Settings

“…Budding yeasts of the subphylum Saccharomycotina are distributed across a wide range of habitats (1–3), including as commensals in the human microbiota (1, 4). However, under rare circumstances, yeasts can cause candidiasis, which is an infection caused by yeasts often assigned to the genus Candida and considered opportunistic pathogens (5).…”

“…Understanding the ecology of pathogenic yeasts is critical to human health for multiple reasons. First, mortality from infections by these yeasts remains high, and candidiasis is the fourth most common hospital-associated bloodstream infection (4, 14, 15). Second, Candida auris recently emerged as a multi-drug resistant opportunistic pathogen, with additional strains exhibiting resistance to many anti-fungal drugs (14, 16).…”

Genomic evidence for a hybrid origin of the yeast opportunistic pathogenCandida albicans

“…Visualizations were performed with IGV(Thorvaldsdóttir, Robinson, and Mesirov 2013).27 Analysis of C. albicans heterozygosity patterns. A) Schematic phylogenetic tree adapted from(Gabaldón and Fairhead 2019) indicating the different C. albicans clades in orange, and a potential common ancestor in red. Strains used for the comparison of heterozygous positions across different clades are indicated, with strains of the same group of analysis being written with the same color (red -group 1, blue -group 2 and grey -group 3); B) Schematic representation of the methodology for the comparison of heterozygous SNPs in heterozygous blocks (grey).…”