Emerging Mechanisms of Drug Resistance in Candida albicans.

Abstract

Drug resistance mechanisms in the commensal human pathogen Candida albicans are continually evolving. Over time, Candida species have implemented diverse strategies to vanquish the effects of various classes of drugs, thereby emanating as a serious life threat. Apart from the repertoire of well-established strategies, which predominantly comprise permeability constraints, increased drug efflux or compromised drug import, alteration, overexpression of drug targets, and chromosome duplication, C. albicans has evolved novel regulatory mechanisms of drug resistance. For instance, recent evidences point to newer circuitry involving different mediators of the stress-responsive machinery of oxidative, osmotic, thermal, nitrosative, and nutrient limitation, which contribute to the emergence of drug resistance. Contemporary advances in genome-wide studies of transcription factors, for instance, the Zn2Cys6 transcription factors, TAC1 (transcriptional activator of CDR) in Candida albicans, or YRR1 in yeast have made it feasible to dissect their involvement for the elucidation of unexplored regulatory network of drug resistance. The coordination of implementers of the conventional and nonconventional drug resistance strategies provides robustness to this commensal human pathogen. In this review, we shed light not only on the established strategies of antifungal resistance but also discuss emerging cellular circuitry governing drug resistance of this human pathogen.