Preprint
The Candida albicans reference strain SC5314 contains a rare, dominant allele of the transcription factor Rob1 that modulates biofilm formation and oral commensalism
bioRxiv
Cold Spring Harbor Laboratory
06/17/2023
DOI: 10.1101/2023.06.17.545405
PMCID: PMC10312810
PMID: 37398495
Abstract
Candida albicans is a diploid human fungal pathogen that displays significant genomic and phenotypic heterogeneity over a range of virulence traits and in the context of a variety of environmental niches. Here, we show that the effects of Rob1 on biofilm and filamentation virulence traits is dependent on both the specific environmental condition and the clinical strain of C. albicans. The C. albicans reference strain SC5314 is a ROB1 heterozygote with two alleles that differ by a single nucleotide polymorphism at position 946 resulting in a serine or proline containing isoform. An analysis of 224 sequenced C. albicans genomes indicates that SC5314 is the only ROB1 heterozygote documented to date and that the dominant allele contains a proline at position 946. Remarkably, the ROB1 alleles are functionally distinct and the rare ROB1946Sallele supports increased filamentation in vitro and increased biofilm formation in vitro and in vivo, suggesting it is a phenotypic gain-of-function allele. SC5314 is amongst the most highly filamentous and invasive strains characterized to date. Introduction of the ROB1946Sallele into a poorly filamenting clinical isolate increases filamentation and conversion of an SC5314 laboratory strain to a ROB1946S homozygote increases in vitro filamentation and biofilm formation. In a mouse model of oropharyngeal infection, the predominant ROB1946P allele establishes a commensal state while the ROB1946S phenocopies the parent strain and invades into the mucosae. These observations provide an explanation for the distinct phenotypes of SC5314 and highlight the role of heterozygosity as a driver of C. albicans phenotypic heterogeneity.
Details
- Title: Subtitle
- The Candida albicans reference strain SC5314 contains a rare, dominant allele of the transcription factor Rob1 that modulates biofilm formation and oral commensalism
- Creators
- Virginia E. Glazier - Niagara UniversityJuraj KramaraTomye OllingerNorma V. Solis - Harbor–UCLA Medical CenterRobert Zarnowski - University of WisconsinRohan S. Wakade - University of IowaMin-Ju Kim - University of GeorgiaGabriel J. WeigelShen-Huan Liang - Brown UniversityRichard J. Bennett - Brown UniversityMelanie Wellington - University of IowaDavid R. Andes - University of Wisconsin–MadisonMark A. Stamnes - University of IowaScott G. Filler - Harbor–UCLA Medical CenterDamian J. Krysan - University of Iowa
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- DOI
- 10.1101/2023.06.17.545405
- PMID
- 37398495
- PMCID
- PMC10312810
- Publisher
- Cold Spring Harbor Laboratory
- Language
- English
- Date posted
- 06/17/2023
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Stead Family Department of Pediatrics; Surgery; Infectious Disease (Pediatrics); Internal Medicine
- Record Identifier
- 9984441854202771
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