Brendan P. Cormack
Genetics of Host-Pathogen Relations in Candida albicans
Candida species are the most important fungal pathogens of humans, causing primarily mucosal infections, which in immunocompromised patients can breach the mucosal barrier and cause life threatening systemic infections. A number of factors, including hyphal formation secretion of hydroytic enzymes, and adherence to host tissue, have been proposed as important to virulence. The details of the host-pathogen interaction are, however, largely unknown, in part because of the difficulties inherent in the genetic analysis of Candida albicans where most studies have focused. We are analyzing fungal virulence in the pathogen Candida glabrata, currently the most frequently isolated fungal species in the ICU in the United States. C. glabrata is haploid and is ideally suited to a genetic analysis of yeast virulence. This organism can be easily manipulated at the molecular level, permitting rapid analysis of even complex multifactorial processes like its interaction with the mammalian host. Our research efforts are focused in two broad screens for genes important in virulence. First, following up on our identification of a novel adhesion mediating adherence to human epithelial cells, we are interested in identifying the multiple adhesions that C. glabrata expresses and to clarify their role in host colonization and persistence. Second, we are screening for mutants unable to persist in animal models of candidiasis. These screens are being carried out directly in animals using a high throughput strategy whereby pools of 96 mutants can be analyzed at once in a single animal.