Comprehensive genetic analysis of adhesin proteins and their role in virulence of Candida albicans

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dc.citation.articleNumberiyab003en_US
dc.citation.issueNumber2en_US
dc.citation.journalTitleGeneticsen_US
dc.citation.volumeNumber217en_US
dc.contributor.authorRosiana, Sierraen_US
dc.contributor.authorZhang, Liyangen_US
dc.contributor.authorKim, Grace H.en_US
dc.contributor.authorRevtovich, Alexey V.en_US
dc.contributor.authorUthayakumar, Deevaen_US
dc.contributor.authorSukumaran, Arjunen_US
dc.contributor.authorGeddes-McAlister, Jenniferen_US
dc.contributor.authorKirienko, Natalia V.en_US
dc.contributor.authorShapiro, Rebecca S.en_US
dc.date.accessioned2021-03-25T18:46:04Zen_US
dc.date.available2021-03-25T18:46:04Zen_US
dc.date.issued2021en_US
dc.description.abstractCandida albicans is a microbial fungus that exists as a commensal member of the human microbiome and an opportunistic pathogen. Cell surface-associated adhesin proteins play a crucial role in C. albicans’ ability to undergo cellular morphogenesis, develop robust biofilms, colonize, and cause infection in a host. However, a comprehensive analysis of the role and relationships between these adhesins has not been explored. We previously established a CRISPR-based platform for efficient generation of single- and double-gene deletions in C. albicans, which was used to construct a library of 144 mutants, comprising 12 unique adhesin genes deleted singly, and every possible combination of double deletions. Here, we exploit this adhesin mutant library to explore the role of adhesin proteins in C. albicans virulence. We perform a comprehensive, high-throughput screen of this library, using Caenorhabditis elegans as a simplified model host system, which identified mutants critical for virulence and significant genetic interactions. We perform follow-up analysis to assess the ability of high- and low-virulence strains to undergo cellular morphogenesis and form biofilms in vitro, as well as to colonize the C. elegans host. We further perform genetic interaction analysis to identify novel significant negative genetic interactions between adhesin mutants, whereby combinatorial perturbation of these genes significantly impairs virulence, more than expected based on virulence of the single mutant constituent strains. Together, this study yields important new insight into the role of adhesins, singly and in combinations, in mediating diverse facets of virulence of this critical fungal pathogen.en_US
dc.identifier.citationRosiana, Sierra, Zhang, Liyang, Kim, Grace H., et al.. "Comprehensive genetic analysis of adhesin proteins and their role in virulence of Candida albicans." <i>Genetics,</i> 217, no. 2 (2021) Oxford University Press: https://doi.org/10.1093/genetics/iyab003.en_US
dc.identifier.doihttps://doi.org/10.1093/genetics/iyab003en_US
dc.identifier.urihttps://hdl.handle.net/1911/110196en_US
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the authors.en_US
dc.titleComprehensive genetic analysis of adhesin proteins and their role in virulence of Candida albicansen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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