Candida albicans Biofilms, Heterogeneity and Antifungal Drug Tolerance

Candida albicans is a pathogenic member of the human oral and gastrointestinal microbiota. Biofilms of C. albicans form on indwelling devices, such as catheters and heart valves, and recent evidence suggests that biofilms also form on the mucosal surfaces of the mouth and vagina. Biofilm infections of prosthetic devices are untreatable by antifungals and infections of the mucosa are frequently difficult to treat and recurrent. The recent characterizations of the attachment mediated tolerance of persister cells to amphotericin B and calcineurin-Hsp90 based tolerance to azole antifungals have helped to shed light on the recalcitrant nature of C. albicans infections. In this review, the refractory nature of Candida infections to antifungals will be examined through the context of biofilms, heterogeneity and drug tolerance. Understanding the mechanisms of biofilm drug tolerance and phenotypic heterogeneity may lead to the development of the first antifungal drugs capable of eradicating infection, salvaging medical devices, and preventing