Adaptation to the dietary sugar D-tagatose via genome instability in polyploid Candida albicans cells

Abstract

The opportunistic fungal pathogen Candida albicans undergoes an unusual parasexual cycle wherein diploid cells mate to form tetraploid cells that can generate genetically diverse progeny via a non-meiotic program of chromosome loss. The genetic diversity afforded by parasex impacts clinically relevant features including drug resistance and virulence, and yet the factors influencing genome instability in C. albicans are not well defined. To understand how environmental cues impact genome instability, we monitored ploidy change following tetraploid cell growth in a panel of different carbon sources. We found that growth in one carbon source, D-tagatose, led to high levels of genomic instability and chromosome loss in tetraploid cells. This sugar is a stereoisomer of L-sorbose which was previously shown to promote karyotypic changes in C. albicans. However, while expression of the SOU1 gene enabled utilization of L-sorbose, overexpression of this gene did not promote growth in D-tagatose, indicating differences in assimilation of the two sugars. In addition, genome sequencing of multiple progeny recovered from D-tagatose cultures revealed increased relative copy numbers of chromosome 4, suggestive of chromosome-level regulation of D-tagatose metabolism. Together, these studies identify a novel environmental cue that induces genome instability in C. albicans, and further implicate chromosomal changes in supporting metabolic adaptation in this species.

Candida albicans Isolates 529L and CHN1 Exhibit Stable Colonization of the Murine Gastrointestinal Tract

“…The nuclear genome sequences and General Feature Files (GFF) for C. albicans SC5314 reference genome (version A22) were downloaded from the Candida Genome Database ( http://www.candidagenome.org/ ). Alignment, coverage, ploidy, heterozygosity, and variant calling were performed as previously described ( 84 ). Average coverage levels for SC5314, 529L, and CHN1 were 141×, 466×, and 245×, respectively.…”

Candida albicans Isolates 529L and CHN1 Exhibit Stable Colonization of the Murine Gastrointestinal Tract

“…The nuclear genome sequences and General Feature Files (GFF) for C. albicans SC5314 reference genome (version A22) were downloaded from the Candida Genome Database (http://www.candidagenome.org/). Alignment, coverage, ploidy, heterozygosity and variant calling were performed as previously described (77). Average coverage levels for SC5314, 529L and CHN1 were 141X, 466X and 245X, respectively.…”