Comparative genomics of emerging pathogens in the Candida glabrata clade.

The CTG clade comprises the majority of Candida species and forms a monophyletic group of yeasts that exhibit a genetic code transition, causing the codon CTG to be translated as serine instead of leucine.

“The CTG clade comprises the majority of Candida species and forms a monophyletic group of yeasts that exhibit a genetic code transition, causing the codon CTG to be translated as serine instead of leucine [60–62]”

The C. glabrata genome harbors several members of a specific gene family encoding epithelial adhesin proteins (EPA genes), which are considered a key factor in its ability to infect humans.

“The C. glabrata genome harbors several members of a specific gene family encoding epithelial adhesin proteins (EPA genes), which are considered a key factor in its ability to infect humans (Cormack and Falkow, 1999; Roetzer et al., 2011; Gabaldón et al., 2013; Vale-Silva et al., 2017).”

C. glabrata may have acquired a unique set of pathogenesis attributes.

“As the capability to infect humans appears to have emerged independently within the Nakaseomyces [18], C. glabrata may have acquired a unique set of pathogenesis attributes.”

Molecular phylogenetic and genome analysis have revealed that the three human pathogenic species of the glabrata group, C. glabrata, C. nivariensis and C. bracarenses, are polyphyletic in origin.

“Intriguingly, molecular phylogenetic and genome analysis have revealed three human pathogenic species, C. glabrata, C. nivariensis and C. bracarenses of the glabrata group, to be polyphyletic in origin [18,25].”

Evolutionarily, C. glabrata is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to C. albicans.

“Evolutionarily, it is closer to the non-pathogenic yeast Saccharomyces cerevisiae than to the most prevalent Candida bloodstream pathogen, C. albicans.”

The capability to infect humans appears to have emerged independently within the Nakaseomyces.

“As the capability to infect humans appears to have emerged independently within the Nakaseomyces [18], C. glabrata may have acquired a unique set of pathogenesis attributes.”

C. albicans belongs to the CTG clade wherein the CTG codon is translated as serine instead of leucine.

“Contrarily, C. albicans belongs to the CTG clade wherein the CTG codon is translated as serine instead of leucine [17,18].”

C. glabrata belongs to the non-CTG Saccharomycetaceae clade in which the CTG codon encodes leucine.

“C. glabrata is a haploid budding yeast, and belongs to the non-CTG, Saccharomycetaceae clade in which the CTG codon encodes leucine [17,18].”

Both C. glabrata and S. cerevisiae belong to the Whole Genome Duplication (WGD) group.

“Both C. glabrata and S. cerevisiae belong to the Whole Genome Duplication (WGD) group, and are assumed to have arisen from the same tetraploid hybrid ancestor, which existed about 100-200 million years ago [18].”

Within the Saccharomycetaceae family, C. glabrata belongs to the genus Nakaseomyces, which contains three pathogenic species and three environmental species.

“As mentioned earlier, within the Saccharomycetaceae family, C. glabrata belongs to the genus Nakaseomyces, which contains three pathogenic species (C. glabrata, C. nivariensis and C. bracarenses) and three environmental species (C. castellii, Kluyveromyces delphensis and K. bacillisporus) [18].”

Compared to the S. cerevisiae lineage, a greater degree of gene loss has occurred in the C. glabrata lineage.

“Furthermore, compared to the S. cerevisiae lineage, a greater degree of gene loss has occurred in the C. glabrata lineage [17,18].”

Nakaseomyces is the only group that possesses the ability to infect humans among the post-WGD clade.

“Furthermore, Nakaseomyces is the only group that possesses the ability to infect humans among the post-WGD clade, and, recently identified C. bracarensis and C. nivariensis are the pathogenic close relatives of C. glabrata [18].”

C. glabrata is a haploid budding yeast that predominantly reproduces clonally.

“C. glabrata is a haploid budding yeast that predominantly reproduces clonally.”

Expansion of the EPA gene family is linked with virulence of the fungal species of the Nakaseomyces clade.

“Recent analysis has linked expansion of the EPA gene family with virulence of the fungal species of the Nakaseomyces clade, with C. glabrata, C. bracarensis, C. nivariensis and K. delphensis containing 17–23, 12, 9 and 1 Epa adhesins, respectively [18].”

Nicotinic acid auxotrophy is a trait of the Nakaseomyces clade, which contains both environmental and pathogenic species.

“The loss of nicotinic acid synthesis genes was thought to be due to close association of C. glabrata with the mammalian host, however, recent studies report that the nicotinic acid auxotrophy is a trait of the Nakaseomyces clade, which contains both environmental and pathogenic species [18].”

C. glabrata has a set of six conserved duplicated gene paralogs encoding glycolytic enzymes, Eno1/Eno2, Pyc1/Pyc2, Glk1/Emi2, Hxk1/Hxk2, Tdh2/Tdh3 and Cdc19/Pyk2, that may aid in increased carbon flux through glycolysis and contribute to its respiro-fermentative lifestyle.

“C. glabrata also has a set of six conserved duplicated gene paralogs encoding glycolytic enzymes, Eno1/Eno2, Pyc1/Pyc2, Glk1/Emi2, Hxk1/Hxk2, Tdh2/Tdh3 and Cdc19/Pyk2 [18], that may aid in the increased carbon flux through glycolysis, and contribute to its respiro-fermentative lifestyle [114].”

C. glabrata, as part of the post-WGD Saccharomycetaceae clade, underwent the same process but apparently has maintained a residual Sef1 function, resulting in a hybrid form of iron regulation with major features from S. cerevisiae and minor features from C. albicans and other pathogenic fungi.

“C. glabrata, as part of the post-WGD Saccharomycetaceae clade (53), underwent the same process but apparently has maintained a residual Sef1 function, resulting in a hybrid form of iron regulation with major features derived from the S. cerevisiae system and minor features retained from the system used by C. albicans and other pathogenic fungi.”