Divergent Targets of Candida albicans Biofilm Regulator Bcr1In VitroandIn Vivo

Abstract

ABSTRACTCandida albicansis a causative agent of oropharyngeal candidiasis (OPC), a biofilm-like infection of the oral mucosa. Biofilm formation depends upon theC. albicanstranscription factor Bcr1, and previous studies indicate that Bcr1 is required for OPC in a mouse model of infection. Here we have used a nanoString gene expression measurement platform to elucidate the role of Bcr1 in OPC-related gene expression. We chose for assays a panel of 134 genes that represent a range of morphogenetic and cell cycle functions as well as environmental and stress response pathways. We assayed gene expression in whole infected tongue samples. The results sketch a portrait ofC. albicansgene expression in which numerous stress response pathways are activated during OPC. This one set of experiments identifies 64 new genes with significantly altered RNA levels during OPC, thus increasing substantially the number of known genes in this expression class. Thebcr1Δ/Δ mutant had a much more limited gene expression defect during OPC infection than previously reported forin vitrogrowth conditions. Among major functional Bcr1 targets, we observed thatALS3was Bcr1 dependentin vivowhileHWP1was not. We used null mutants and complemented strains to verify that Bcr1 and Hwp1 are required for OPC infection in this model. The role of Als3 is transient and mild, though significant. Our findings suggest that the versatility ofC. albicansas a pathogen may reflect its ability to persist in the face of multiple stresses and underscore that transcriptional circuitry during infection may be distinct from that detailed duringin vitrogrowth.