Abstract
Candida albicans is an opportunistic pathogen that induces vulvovaginal candidiasis (VVC), among other diseases. In the vaginal environment, the source of carbon for C. albicans can be either lactic acid or its dissociated form, lactate. It has been shown that lactate, similar to the popular antifungal drug fluconazole (FLC), reduces the expression of the ERG11 gene and hence the amount of ergosterol in the plasma membrane. The Cdr1 transporter that effluxes xenobiotics from C. albicans cells, including FLC, is delocalized from the plasma membrane to a vacuole under the influence of lactate. Despite the overexpression of the CDR1 gene and the increased activity of Cdr1p, C. albicans is fourfold more sensitive to FLC in the presence of lactate than when glucose is the source of carbon. We propose synergistic effects of lactate and FLC in that they block Cdr1 activity by delocalization due to changes in the ergosterol content of the plasma membrane.
Highlights
Candida spp. are opportunistic pathogens that cause severe systemic infections in humans, such as vulvovaginal candidiasis (VVC) [1]
Information regarding the mechanism by which lactate exerts its effects on C. albicans cells is scarce; we decided to investigate the susceptibility of C. albicans to FLC
To explain why there was a high sensitivity of C. albicans to FLC observed when grown in the presence of lactate despite an increase in Cdr1 expression and activity, we examined the localization of Cdr1p in the cells
Summary
Candida spp. are opportunistic pathogens that cause severe systemic infections in humans, such as vulvovaginal candidiasis (VVC) [1]. The concentration of acetic acid in the vaginal environment is low, ranging from 1–4 mM [8], while the lactic acid concentration in the vaginal milieu is around 110 mM [9]. Based on their results, Matsubara et al [10] suggested that an antifungal effect occurs only after prolonged incubation with cultures of Lactobacilli (24 or 48 h) in which lactic acid could have accumulated in the medium at the right quantity. C. albicans growing on lactate is more resistant to amphotericin B (AmB), another antifungal drug [15]
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