Borah, S. and Shivarathri, R. and Kaur, Rupinder (2011) The Rho1 GTPase-activating Protein CgBem2 Is Required for Survival of Azole Stress in Candida glabrata. Journal of Biological Chemistry, 286 (39). pp. 34311-34324. ISSN 0021-9258

Preview

Text JBC 286 p34311.pdf Download (4Mb) | Preview

Abstract

Invasive fungal infections are common clinical complications of neonates, critically ill, and immunocompromised patients worldwide. Candida species are the leading cause of disseminated fungal infections, with Candida albicans being the most prevalent species. Candida glabrata, the second/third most common cause of candidemia, shows reduced susceptibility to a widely used antifungal drug fluconazole. Here, we present findings from a screen of 9134 C. glabrata Tn7 insertion mutants for altered survival profiles in the presence of fluconazole. We have identified two components of RNA polymerase II mediator complex, three players of Rho GTPase-mediated signaling cascade, and two proteins implicated in actin cytoskeleton biogenesis and ergosterol biosynthesis that are required to sustain viability during fluconazole stress. We show that exposure to fluconazole leads to activation of the protein kinase C (PKC)-mediated cell wall integrity pathway in C. glabrata. Our data demonstrate that disruption of a RhoGAP (GTPase activating protein) domain-containing protein, CgBem2, results in bud-emergence defects, azole susceptibility, and constitutive activation of CgRho1-regulated CgPkc1 signaling cascade and cell wall-related phenotypes. The viability loss of Cgbem2Δ mutant upon fluconazole treatment could be partially rescued by the PKC inhibitor staurosporine. Additionally, we present evidence that CgBEM2 is required for the transcriptional activation of genes encoding multidrug efflux pumps in response to fluconazole exposure. Last, we report that Hsp90 inhibitor geldanamycin renders fluconazole a fungicidal drug in C. glabrata

Item Type:	Article
Additional Information:	[Open Access from the Publisher]
Depositing User:	Users 2 not found.
Date Deposited:	11 Sep 2015 08:31
Last Modified:	17 Sep 2016 17:31
URI:	http://cdfd.sciencecentral.in/id/eprint/491

Actions (login required)

View Item