IDENTIFICATION AND CHARACTERIZATION OF MOLECULAR DRUG TARGETS IN CANDIDA GLABRATA

Abstract

Fungal infections often contribute to high morbidity and mortality in humans. This requires the attention of researchers to explore the host factors that facilitate the development of disease symptoms, and the mechanism of pathogenesis, as well as to identify the novel drug targets. Candidiasis, a condition resulting from the infection of Candida, ranges from superficial to deeply invasive and systemic infections. Oral thrush and vulvovaginitis are the most common superficial forms of candidiasis, while candidemia (bloodstream infection) is the most common invasive infection. Immune-suppressed state, implantation devices like catheter, parenteral nutrition, and the over-use of antibiotics are common factors that facilitate Candida infection. Candida albicans is a common human pathogen, followed by non-albicans Candida species, e.g., C. glabrata. Candidiasis is known to affect more than 2, 50,000 people worldwide every year and are estimated to cause more than 50,000 deaths annually. As per the report of Center for Disease Control and Prevention, U.S. Department of Health and Human Services, the total economic burden that Candida infections add to the U.S. Healthcare expenditures per year is approximately US$ 8 billion. Increase in the cases of candidiasis, antifungal drugs resistance, and shift in the epidemiology to non-albicans species, have encouraged us to study the effect of an important known host factor, hypoxia (a low oxygen state) upon the pathogenesis, and to identify effective drug targets under hypoxic condition, using functional genomics approaches. The ability of pathogen to survive hypoxia microenvironment of the host tissues during infection remains poorly understood this aspect has also been undertaken in the present study. newlineInvestigations were carried out to explore the role of hypoxia (1%O2 v/v) upon key virulence attributes (e.g., growth, viability, susceptibility to antifungal drug, adhesion and biofilm development, including biofilm susceptibility to existing drugs) of C. albicans and C. gl