Work

Genetic adaptive mechanisms mediating response and tolerance to acetic acid stress in the human pathogen Candida glabrata: role of the CgHaa1-dependent signaling pathway

Year: 2017

Type: conference-paper

Abstract: The increased resilience of Candida glabrata to azoles and the continuous emergence of strains resistant to other antifungals demands the development of new therapeutic approaches focused on non-conventional biological targets. Genes contributing to increase C. glabrata competitiveness in the different infection sites are an interesting and unexplored cohort of therapeutic targets. To thrive in the vaginal tract and avoid exclusion C. glabrata cells have evolved dedicated responses rendering them capable of tolerating multiple environmental challenges, including the presence of acetic and lactic acids produced by the commensal microbiota. In this work a cohort of vaginal clinical isolates were phenotyped for their tolerance to acetic acid stress at a low pH as well as for several traits that are known to influence sensitivity to this organic acid, including the structure of the cell envelope and the ability to consume the acid in the presence of glucose. The role played by the ORF CAGL0L09339g, an homologue of the ScHaa1, a critical regulator of acetic acid resistance in S. cerevisiae[1], in C. glabrata response and tolerance to acetic acid stress at pH 4 was also scrutinized using a transcriptomic analysis. The role of CgHaa1 as well as of several of its target genes in mediating virulence of C. glabrata against epithelial vaginal cells was also studied.

Source: Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)