Vulvovaginal candidiasis, a superficial
infection caused predominantly by the pathogenic fungus Candida albicans, is frequently treated with
clotrimazole. Some
drug formulations contain
lactate for improved solubility.
Lactate may modify C. albicans physiology and
drug sensitivity by serving as a
carbon source for the fungus and/or affecting local pH. Here, we explored the effects of
lactate, in combination with pH changes, on C. albicans proliferation, morphology and
clotrimazole sensitivity. Moreover, we determined the influence of growth phase and morphology per se on
drug sensitivity. We showed that utilization of
lactate as a
carbon source did not promote fast fungal proliferation or filamentation.
Lactate had no influence on
clotrimazole-mediated killing of C. albicans in standard fungal cultivation medium but had an additive effect on the fungicidal
clotrimazole action under in vitro vagina-simulative conditions. Moreover,
clotrimazole-mediated killing was growth-phase and morphology dependent. Post-exponential cells were resistant to the fungicidal action of
clotrimazole, whilst logarithmic cells were sensitive, and hyphae showed the highest susceptibility. Finally, we showed that treatment of pre-formed C. albicans hyphae with sublethal concentrations of
clotrimazole induced a reversion to yeast-phase growth. As C. albicans hyphae are considered the pathogenic morphology during mucosal
infections, these data suggest that elevated fungicidal activity of
clotrimazole against hyphae plus
clotrimazole-induced hyphae-to-yeast reversion may help to dampen acute vaginal
infections by reducing the relative proportion of hyphae and thus shifting to a non-invasive commensal-like population. In addition,
lactate as an ingredient of
clotrimazole formulations may potentiate
clotrimazole killing of C. albicans in the vaginal microenvironment.