Strain background of Candida albicans interacts with SIR2 to alter phenotypic switching

Andrew L. Woodruff, Judith Berman, Matthew Anderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The genetic background between strains of a single species and within a single strain lineage can significantly impact the expression of biological traits. This genetic variation may also reshape epigenetic mechanisms of cell identity and environmental responses that are controlled by interconnected transcriptional networks and chromatin-modifying enzymes. Histone deacetylases, including sirtuins, are critical regulators of chromatin state and have been directly implicated in governing the phenotypic transition between the ‘sterile’ white state and the mating-competent opaque state in Candida albicans, a common fungal commensal and pathogen of humans. Here, we found that a previously ambiguous role for the sirtuin SIR2 in C. albicans phenotypic switching is likely linked to the genetic background of mutant strains produced in the RM lineage of SC5314. SIR2 mutants in a specific lineage of BWP17 displayed increased frequencies of switching to the opaque state compared to the wild-type. Loss of SIR2 in other SC5314-derived backgrounds, including newly constructed BWP17 sir2Δ/Δ mutants, failed to recapitulate the increased white–opaque switching frequencies observed in the original BWP17 sir2Δ/Δ mutant background. Whole-genome sequencing revealed the presence of mul-tiple imbalanced chromosomes and large loss of heterozygosity tracts that likely interact with SIR2 to increase phenotypic switching in this BWP17 sir2Δ/Δ mutant lineage. These genomic changes are not found in other SC5314-derived sir2Δ/Δ mutants that do not display increased opaque cell formation. Thus, complex karyotypes can emerge during strain construction that modify mutant phenotypes and highlight the importance of validating strain background when interpreting phenotypes.

Original languageEnglish
Article number001444
JournalMicrobiology (United Kingdom)
Volume170
Issue number3
DOIs
StatePublished - 2024

Funding

FundersFunder number
National Science Foundation2046863, 1F31AI167576
National Institutes of HealthR01AI148788

    Keywords

    • aneuploidy
    • Candida
    • epigenetics
    • white opaque switching

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