Abstract
Candida glabrata is considered a major opportunistic fungal pathogen of humans. The capacity of this yeast species to cause infections is dependent on the ability to grow within the human host environment and to assimilate the carbon sources available. Previous studies have suggested that C. albicans can encounter glucose-poor microenvironments during infection and that the ability to use alternative non-fermentable carbon sources, such as carboxylic acids, contributes to the virulence of this fungus. Transcriptional studies on C. glabrata cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analyzing biofilm formation, antifungal drug resistance, and phagocytosis of C. glabrata cells grown in the presence of acetic acid as an alternative carbon source. C. glabrata planktonic cells grown in media containing acetic acid were more susceptible to fluconazole and were better phagocytosed and killed by macrophages than when compared to media lacking acetic acid. Growth in acetic acid also affected the ability of C. glabrata to form biofilms. The genes ADY2a, ADY2b, FPS1, FPS2, and ATO3, encoding putative carboxylate transporters, were upregulated in C. glabrata planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with fps1 and ady2a mutant strains suggested a potential role of FPS1 and ADY2a in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of C. glabrata infections, in particular in vaginal candidiasis.
Highlights
Candida glabrata is a prevalent human fungal pathogen that has become the second most frequent cause of candidiasis after Candida albicans in the United States, according to the SENTRY Program (Pfaller et al, 2001, 2011)
We obtained lower fluconazole Minimal Inhibitory Concentration (MIC) and minimal fungicidal concentration (MFC) values (50 and 150 μg/ml, respectively; Table 3). These results show that acetic acid enhances the susceptibility of C. glabrata cells to fluconazole
The Carbon Source Affects C. glabrata Interaction with Phagocytic Cells Since our data suggested that cells grown in media containing acetic acid are more susceptible to fluconazole, we evaluated how macrophages interacted with C. glabrata cells previously grown either in RPMI or RPMI with acetic acid
Summary
Candida glabrata is a prevalent human fungal pathogen that has become the second most frequent cause of candidiasis after Candida albicans in the United States, according to the SENTRY Program (Pfaller et al, 2001, 2011). Both species are commensal colonizers of mucosal surfaces. C. glabrata colonizes host tissues as well as abiotic surfaces as biofilms (Silva et al, 2009). The formation of Candida biofilms raises important clinical issues because of a significant further increase in antifungal drug resistance as well as evasion of host immune defenses. Biofilm formation on medical devices can cause the failure of the device and can serve as a reservoir or source for future continuing infections (Douglas, 2003; Ramage et al, 2005; Calderone and Clancy, 2012)
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