Candida glabrata Ste20 is involved in maintaining cell wall integrity and adaptation to hypertonic stress, and is required for wild‐type levels of virulence

Abstract

The conserved family of fungal Ste20 p21-activated serine-threonine protein kinases regulate several signalling cascades. In Saccharomyces cerevisiae Ste20 is involved in pheromone signalling, invasive growth, the hypertonic stress response, cell wall integrity and binds Cdc42, a Rho-like small GTP-binding protein required for polarized morphogenesis. We have cloned the STE20 homologue from the fungal pathogen Candida glabrata and have shown that it is present in a single copy in the genome. Translation of the nucleotide sequence predicts that C. glabrata Ste20 contains a highly conserved p21-activated serine-threonine protein kinase domain, a binding site for G-protein β subunits and a regulatory Rho-binding domain that enables the kinase to interact with Cdc42 and/or Rho-like small GTPases. C. glabrata Ste20 has 53% identity and 58% predicted amino acid similarity to S. cerevisiae Ste20 and can complement both the nitrogen starvation-induced filamentation and mating defects of S. cerevisiae ste20 mutants. Analysis of ste20 null and disrupted strains suggest that in C. glabrata Ste20 is required for a fully functional hypertonic stress response and intact cell wall integrity pathway. C. glabrata Ste20 is not required for nitrogen starvation-induced filamentation. Survival analysis revealed that C. glabrata ste20 mutants, while still able to cause disease, are mildly attenuated for virulence compared to reconstituted STE20 cells.

Environmental Sensing and Signal Transduction Pathways Regulating Morphopathogenic Determinants of Candida albicans

“…1). The C. albicans MAPKK kinase (MAPKKK) Ste11 has not been characterized in detail, although its homolog in C. glabrata functionally complements an S. cerevisiae Ste11 mutant (51). The transcription factor Ste12 functions downstream of the pheromone-responsive MAPK cascade in budding yeast through a heptamer sequence, TGAAACA, called the pheromone response element (PRE).…”

Hosting Infection: Experimental Models to AssayCandidaVirulence

“…However, because immunosuppression may allow invasive disease to develop in C. glabrata -infected mice, these treatments have been added to an infection model used in some studies to compare the virulence of genetically modified C. glabrata , with fungal burdens used as the virulence estimate [88, 101, 102, 105]. The immunosuppressed mouse infection model has demonstrated the importance of hypertonic stress responses, the cell wall integrity pathway, and nitrogen starvation responses in C. glabrata virulence [103, 104, 106]. In addition, this model has identified a petite mutant, strains expressing hyperactive alleles of the transcription factor gene PDR1 and the ace2 null mutant as being more virulent than their parent strains [88, 105, 121].…”

Fungal Sex and Pathogenesis

“…The transcription factor Cph1 (an ortholog of Ste12) acts together with Efg1, and cph1/efg1 double mutants do not filament and are avirulent in many models of infection (156). STE20 and STE12 are also required for virulence of C. glabrata (41,42). In Cr.…”