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© Research
Publication : Proceedings of the National Academy of Sciences of the United States of America

Aneuploidy and gene dosage regulate filamentation and host colonization by Candida albicans.

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Proceedings of the National Academy of Sciences of the United States of America - 14 Mar 2023

Kakade P, Sircaik S, Maufrais C, Ene IV, Bennett RJ

Link to Pubmed [PMID] – 36893271

Link to DOI – 10.1073/pnas.2218163120

Proc Natl Acad Sci U S A 2023 Mar; 120(11): e2218163120

Aneuploidy is a frequent occurrence in fungal species where it can alter gene expression and promote adaptation to a variety of environmental cues. Multiple forms of aneuploidy have been observed in the opportunistic fungal pathogen Candida albicans, which is a common component of the human gut mycobiome but can escape this niche and cause life-threatening systemic disease. Using a barcode sequencing (Bar-seq) approach, we evaluated a set of diploid C. albicans strains and found that a strain carrying a third copy of chromosome (Chr) 7 was associated with increased fitness during both gastrointestinal (GI) colonization and systemic infection. Our analysis revealed that the presence of a Chr 7 trisomy resulted in decreased filamentation, both in vitro and during GI colonization, relative to isogenic euploid controls. A target gene approach demonstrated that NRG1, encoding a negative regulator of filamentation located on Chr 7, contributes to increased fitness of the aneuploid strain due to inhibition of filamentation in a gene dosage-dependent fashion. Together, these experiments establish how aneuploidy enables the reversible adaptation of C. albicans to its host via gene dosage-dependent regulation of morphology.

https://pubmed.ncbi.nlm.nih.gov/36893271