Proteomic analysis of the pH response in the fungal pathogen Candida glabrata

Abstract

Micro-organisms must adapt to environmental change to survive, and this is particularly true for fungal pathogens such as Candida glabrata. C. glabrata is found both in the environment and in diverse niches in its human host. The ambient pH of these niches varies considerably, and therefore we have examined the response of C. glabrata to changes in ambient pH using a proteomic approach. Proteins expressed in C. glabrata cells growing at pH 4.0, 7.4 or 8.0 were compared by 2-DE, and 174 spots displaying reproducible and statistically significant changes in expression level were identified by peptide mass fingerprinting, thereby extending our 2-DE map of the C. glabrata proteome to a total of 272 identified spots. Proteins involved in glucose metabolism, the TCA cycle, respiration and protein synthesis were expressed at lower levels during growth at pH 7.4 and/or 8.0, whereas proteins involved in stress responses and protein catabolism were expressed at higher levels under these alkaline conditions. Our data suggest that C. glabrata perceives low pH as less stressful than higher pH. This contrasts with another opportunistic fungal pathogen of humans, Candida albicans.

Detailed comparison of Candida albicans and Candida glabrata biofilms under different conditions and their susceptibility to caspofungin and anidulafungin

“…Many studies in vitro have reported the use of a multitude of media, substrates and techniques to study biofilms (Biswas & Chaffin, 2005;Schmidt et al, 2008;Uppuluri et al, 2009). Here, we compared the effect of two commonly used media, namely RPMI 1640 and YNB, at two different pH values (pH 5.6 and 7.0) on C. glabrata and C. albicans adhesion and mature biofilm development.…”

“…We also elucidated the effect of pH 5.6 and 7.0 during biofilm development, because adaptation to changes in pH during biofilm formation is crucial not only for its development, but also for survival of microbial communities at colonized host sites (Schmidt et al, 2008) as well as on medical devices (Ramage et al, 2006). The two media tested, YNB and RPMI 1640, have remained favourite choices for in vitro biofilm formation (Biswas & Chaffin, 2005;Cateau et al, 2008;Chandra et al, 2001).…”

“…Additionally, pH plays an important role, as Candida spp. may colonize different niches with respect to the environmental pH (Biswas & Chaffin, 2005;Schmidt et al, 2008). To date, there is no strict recommendation for a specific medium suitable for in vitro biofilm experiments that would strictly resemble the composition of the human fluids surrounding the device in vivo.…”

Proteomic Studies of the Effects of Different Stress Conditions on Central Carbon Metabolism in Microorganisms

“…Proteomic analysis (2-DE) of C. glabrata in response to changes in ambient pH (4.0, 7.4 or 8.0) [73] reveal a statistically significant change in protein expression level. Peptide mass fingerprinting identified proteins involved in glucose metabolism, the TCA cycle, respiration and protein synthesis to have decreased expression during growth at pH 7.4 and/or 4.0, whereas proteins involved in stress responses and protein catabolism were preferentially expressed under alkaline (pH 8.0) conditions.…”

“…Adaptation to and tolerance of bile stress are important limiting [73] Candida glabrata Different pH pH 7. factors to ensure survival of bifidobacteria in the intestinal environment of humans. The effect of bile salts on protein expression patterns of Bifidobacterium longum has been examined by using proteomic analyses [51] with the identification of 34 differentially regulated proteins, the majority of which were induced after both a minor (0.6 g/1) and a major (1.2 g/l) exposure to bile.…”