High-content phenotypic screenings to identify inhibitors of Candida albicans biofilm formation and filamentation

Abstract

Candida species represent the main cause of opportunistic fungal infections worldwide, and Candida albicans remains the most common etiological agent of candidiasis, now the third to fourth most common nosocomial infection. These infections are typically associated with high morbidity and mortality, mainly due to the limited efficacy of current antifungal drugs. In C. albicans, morphogenetic conversions between yeast and filamentous forms and biofilm formation represent two important biological processes that are intimately associated with the biology of this fungus and also play important roles during the pathogenesis of candidiasis. We have performed cell-based phenotypic screens using three different chemical libraries from the National Cancer Institute's Open Chemical Repository collection and identified several compounds with inhibitory activity against C. albicans biofilm formation and/or filamentation. These phenotype-based approaches represent a prosperous alternative to conventional genetics and genomics techniques to address experimentally challenging and complex biological phenomena, such as biofilm formation and filamentation, while at the same time opening new possibilities for the development of new antifungal agents.

Keywords: Candida albicans; biofilms; chemical library; filamentation; high-content screening.