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Targeted Changes of the Cell Wall Proteome Influence Ability to Form Single- and Multi-strain Biofilms
Candida albicans is the most prevalent human fungal pathogen. Its ability to cause disease relies, in part, on the formation of biofilms, a protective structure of highly adherent cells tolerant to antifungal agents and the host immune response. The biofilm is considered as a persistent root of infection, disseminating infectious cells to other locations. In this study, we performed large-scale phenotypic analyses aimed at identifying genes whose overexpression affects biofilm development in C. albicans. Our screen relied on a collection of 531 C. albicans strains, each conditionally overexpressing one given gene and carrying one specific molecular tag allowing the quantification of strain abundance in mixed-population experiments. Our results strikingly revealed the enrichment of strains overproducing poorly-characterized surface proteins called Pgas (Putative GPI-Anchored proteins), within a 531-strain-containing biofilm model. We show that these PGA genes differentially contribute to single-strain and multi-strain biofilm formation and are involved in specific stages of the biofilm developmental process. Taken together, our results reveal the importance of C. albicans cell surface proteins during biofilm formation and reflect the powerful use of strain barcoding in combination with gene overexpression to identify genes and/or pathways involved in processes pertaining to virulence of pathogenic microbes.
Vyšlo v časopise: Targeted Changes of the Cell Wall Proteome Influence Ability to Form Single- and Multi-strain Biofilms. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004542
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004542Souhrn
Candida albicans is the most prevalent human fungal pathogen. Its ability to cause disease relies, in part, on the formation of biofilms, a protective structure of highly adherent cells tolerant to antifungal agents and the host immune response. The biofilm is considered as a persistent root of infection, disseminating infectious cells to other locations. In this study, we performed large-scale phenotypic analyses aimed at identifying genes whose overexpression affects biofilm development in C. albicans. Our screen relied on a collection of 531 C. albicans strains, each conditionally overexpressing one given gene and carrying one specific molecular tag allowing the quantification of strain abundance in mixed-population experiments. Our results strikingly revealed the enrichment of strains overproducing poorly-characterized surface proteins called Pgas (Putative GPI-Anchored proteins), within a 531-strain-containing biofilm model. We show that these PGA genes differentially contribute to single-strain and multi-strain biofilm formation and are involved in specific stages of the biofilm developmental process. Taken together, our results reveal the importance of C. albicans cell surface proteins during biofilm formation and reflect the powerful use of strain barcoding in combination with gene overexpression to identify genes and/or pathways involved in processes pertaining to virulence of pathogenic microbes.
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