Molecular mechanisms of Amphotericin B resistance in Candida
Candida albicans and several other Candida species are present as benign commensals in one or more body locations in a majority of healthy humans. However, especially in immunocompromised patients, Candida becomes an opportunistic pathogen that can cause superficial as well as severe, life-threatening systemic infections. There is also an increase in the number of clinical isolates resistant to amphotericin B, a frontline antifungal, frequently resulting in treatment failures. Hence, we are trying to identify and characterize genes and regulatory pathway(s) that are involved in amphotericin B resistance. A molecular level understanding of this phenomenon is likely to help in devising strategies to minimize development of resistance during therapy. Besides the above, we have also developed novel molecular genetic tools for conditional expression of C. albicans genes, which will facilitate rapid determination of gene function in this species.
Metabolic engineering of yeast for ethanol production
Fermentative production of ethanol from renewable biomass is an attractive source of energy. A thermotolerant yeast strain that can efficiently ferment sugars from raw materials such as molasses, at up to 38°C, was developed and patented by us earlier. However, this strain, like other S. cerevisiae strains, can not ferment xylose. Xylose can constitute as much as thirty percent of biomass, and its efficient fermentation is critical for cost effective production of ethanol. Thus, in collaboration with other groups at IMTECH, we are engineering the thermotolerant strain for xylose fermentation by introducing genes encoding two enzymatic steps of xylose metabolic pathway from another yeast species. The xylulose kinase of S. cerevisiae is also being overexpressed by replacing its promoter with a strong constitutive promoter. Substantial progress has already been made in constructing such a strain. Work is underway to improve this strain further for efficient fermentation of xylose.