Multidrug resistance in yeast Candida

Abstract

The opportunistic human pathogens Candida albicans and other non-albicans species have acquired considerable significance in the recent past due to the enhanced susceptibility of immunocompromised patients. These pathogenic species of Candida derive their importance not only from the severity of their infections but also from their ability to develop resistance against antifungals. Widespread and prolonged use of azoles has led to the rapid development of the phenomenon of multidrug resistance (MDR), which poses a major hurdle in antifungal therapy. Various mechanisms that contribute to the development of MDR have been implicated in Candida as well as in other human fungal pathogens, and some of these include overexpression of or mutations in the target enzyme of azoles, lanosterol 14 alpha-demethylase, and transcriptional activation of genes encoding drug efflux pump proteins belonging to ATP-binding cassette (ABC) as well as to major facilitator superfamilies (MFS) of transporters. The ABC transporters, CDR1, CDR2, and an MFS pump CaMDR1, play a key role in azole resistance as deduced from their high level of expression found in several azole-resistant clinical isolates.