Candida albicans is part of the human mycobiota, coexisting with the plethora of bacterial species within the gut.
To better understand how C. albicans efficiently establishes gastrointestinal (GI)-tract colonization, we competitively challenged growth of 579 signature-tagged C. albicans strains (∼ 10% genome coverage), each conditionally overexpressing a single gene, in the gut of a mouse model of GI-tract colonization.
Our screen identified CRZ2, a Candida-specific zinc finger transcription factor of the C2H2 family, whose overexpression increased C. albicans intestinal colonization. Using an ex vivo model of Candida-colon explant adhesion assay, we further showed that CRZ2 overexpression imparts increased adhesion of C. albicans to colonic tissue. Genome-wide expression and location experiments revealed that Crz2p directly modulates the expression of many C. albicans mannosyltransferase and cell-wall protein-encoding genes and has dual transcriptional regulatory functions, acting as both activator and repressor of gene expression. Gene-set enrichment analyses indicated that CRZ2 overexpression triggers a substantial reprogramming of amino acid and metal/ion homeostases, while respectively turning on and off the hypoxic and oxidative respiration transcriptional programs.
Our study reflects the powerful use of gene overexpression as a complementary approach to gene deletion to identify relevant biological circuits involved in C. albicans commensalism and links transcriptional regulation of cell-surface proteins to C. albicans ability to thrive within the host.El texto completo de este artículo está disponible en PDF.