Pathogenic yeasts from the genus Candida can cause serious
infection in humans particularly, in immunocompromised patients and are now recognized as major agents of hospital acquired (
nosocomial) infections. In the recent years, there has been a marked increase in the incidence of treatment failures in
candidiasis patients receiving long-term antifungal
therapy, which has posed a serious problem in its successful use in
chemotherapy. Candida cells acquire drug resistance (MDR) during the course of the treatment. The mechanisms of resistance to
azole antifungal agents have been elucidated in Candida species and can be mainly categorized as (i) changes in the cell wall or plasma membrane, which lead to impaired
drug (
azole) uptake; (ii) alterations in the affinity of the
drug target Erg11p (lanosterol 14alpha-demethylase) especially to
azoles or in the cellular content of Erg11p due to target site mutation or overexpression of the ERG11 gene; and (iii) the efflux of drugs mediated by
membrane transport proteins belonging to the
ATP-binding cassette (
ABC) transporters, namely CDR1 and CDR2 or to the major facilitator superfamily (MFS) transporter, CaMDR1. Many such manifestations are associated with the formation of Candida biofilms including those occurring on devices like indwelling intravascular
catheters. Biofilm-associated Candida show uniform resistance to a wide spectrum of antifungal drugs. A combination of different resistance mechanisms is responsible for drug resistance in clinical isolates of Candida species.