Author:

Abstract:

The cAMP-PKA pathway is affecting virulence in many important pathogenic fungi like Candida albicans, Cryptococcus neoformans and Magnaporthe grisea. We provide the first evidence that this is also true for Candida glabrata, an emerging pathogen that is often tolerant to azole drugs and therefore difficult to treat clinically. Adhesion to surfaces is an important virulence factor in C. glabrata, a species that cannot form filaments. Cell wall proteins mediate this process and the C. glabrata genome encodes for at least 67 of these adhesins, but up until now only a limited number of genes (e.g. EPA genes) have been investigated. We have found that the cAMP-PKA pathway in C. glabrata affects the adhesion process. Wild type cells adhere much less to a polystyrene surface in presence of glucose, fructose or sucrose compared to e.g. galactose, a non-cAMP inducing sugar. Deletion of CgGPR1 results in an increased adherence, while a point mutation in CgGPA2 that constitutively activates the cAMP-PKA pathway, results in a strain with very low adhesion capacity. Interestingly, the expresssion of some EPA genes is induced by the cAMP-inducing sugars in a CgGpr1 dependent manner. Taken together, these results indicate that sugars regulate adhesion through the cAMP-PKA pathway in C. glabrata. Why induction of the PKA pathway results in less adhesion and wether this affects virulence remains to be investigated.