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© Research
Publication : Cell host & microbe

Hemizygosity Enables a Mutational Transition Governing Fungal Virulence and Commensalism

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell host & microbe - 01 Jan 2019

Liang SH, Anderson MZ, Hirakawa MP, Wang JM, Frazer C, Alaalm LM, Thomson GJ, Ene IV, Bennett RJ

Link to Pubmed [PMID] – 30824263

Link to DOI – S1931-3128(19)30042-310.1016/j.chom.2019.01.005

Cell Host Microbe 2019 03; 25(3): 418-431.e6

Candida albicans is a commensal fungus of human gastrointestinal and reproductive tracts, but also causes life-threatening systemic infections. The balance between colonization and pathogenesis is associated with phenotypic plasticity, with alternative cell states producing different outcomes in a mammalian host. Here, we reveal that gene dosage of a master transcription factor regulates cell differentiation in diploid C. albicans cells, as EFG1 hemizygous cells undergo a phenotypic transition inaccessible to “wild-type” cells with two functional EFG1 alleles. Notably, clinical isolates are often EFG1 hemizygous and thus licensed to undergo this transition. Phenotypic change corresponds to high-frequency loss of the functional EFG1 allele via de novo mutation or gene conversion events. This phenomenon also occurs during passaging in the gastrointestinal tract with the resulting cell type being hypercompetitive for commensal and systemic infections. A “two-hit” genetic model therefore underlies a key phenotypic transition in C. albicans that enables adaptation to host niches.

https://pubmed.ncbi.nlm.nih.gov/30824263