AUTHOR=Mota Sandra , Alves Rosana , Carneiro Catarina , Silva Sónia , Brown Alistair J. , Istel Fabian , Kuchler Karl , Sampaio Paula , Casal Margarida , Henriques Mariana , Paiva Sandra 

TITLE=Candida glabrata susceptibility to antifungals and phagocytosis is modulated by acetate

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00919

DOI=10.3389/fmicb.2015.00919

ISSN=1664-302X

ABSTRACT=<p><italic>Candida glabrata</italic> 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 <italic>C. albicans</italic> 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 <italic>C. glabrata</italic> cells identified a similar response, upon nutrient deprivation. In this work, we aimed at analyzing biofilm formation, antifungal drug resistance, and phagocytosis of <italic>C. glabrata</italic> cells grown in the presence of acetic acid as an alternative carbon source. <italic>C. glabrata</italic> 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 <italic>C. glabrata</italic> to form biofilms. The genes <italic>ADY2a, ADY2b, FPS1, FPS2</italic>, and <italic>ATO3</italic>, encoding putative carboxylate transporters, were upregulated in <italic>C. glabrata</italic> planktonic and biofilm cells in the presence of acetic acid. Phagocytosis assays with <italic>fps1</italic> and <italic>ady2a</italic> mutant strains suggested a potential role of <italic>FPS1</italic> and <italic>ADY2a</italic> in the phagocytosis process. These results highlight how acidic pH niches, associated with the presence of acetic acid, can impact in the treatment of <italic>C. glabrata</italic> infections, in particular in vaginal candidiasis.</p>