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

Journal Article · · G3
 [1];  [1];  [2];  [1];  [3]
  1. Brown University, Providence, RI (United States)
  2. Brown University, Providence, RI (United States); Sandia National Laboratories (SNL-CA), Livermore, CA (United States)
  3. Brown University, Providence, RI (United States); Pasteur Institute, Paris (France)

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 nonmeiotic 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 progenies 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.

Research Organization:
Sandia National Laboratories (SNL-CA), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); National Institutes of Health (NIH)
Grant/Contract Number:
NA0003525
OSTI ID:
2471774
Journal Information:
G3, Journal Name: G3 Journal Issue: 7 Vol. 11; ISSN 2160-1836
Publisher:
Genetics Society of AmericaCopyright Statement
Country of Publication:
United States
Language:
English

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