Genome-Wide Response to Drugs and Stress in the Pathogenic Yeast Candida glabrata.

Abstract

Candida glabrata is the second most common cause of candidemia worldwide and its prevalence has continuously increased over the last decades. C. glabrata infections are especially worrisome in immunocompromised patients, resulting in serious systemic infections, associated to high mortality rates. Intrinsic resistance to azole antifungals, widely used drugs in the clinical setting, and the ability to efficiently colonize the human host and medical devices, withstanding stress imposed by the immune system, are thought to underlie the emergence of C. glabrata. There is a clear clinical need to understand drug and stress resistance in C. glabrata. The increasing prevalence of multidrug resistant isolates needs to be addressed in order to overcome the decrease of viable therapeutic strategies and find new therapeutic targets. Likewise, the understanding of the mechanisms underlying its impressive ability thrive under oxidative, nitrosative, acidic and metabolic stresses, is crucial to design drugs that target these pathogenesis features. The study of the underlying mechanisms that translate C. glabrata plasticity and its competence to evade the immune system, as well as survive host stresses to establish infection, will benefit from extensive scrutiny. This chapter provides a review on the contribution of genome-wide studies to uncover clinically relevant drug resistance and stress response mechanisms in the human pathogenic yeast C. glabrata.