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.
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