Research Projects

In recent decades antimicrobial resistance is sharply increasing and become a major threat to public health. Global mortality rates are increasing by invasive fungal infections that exceed that of tuberculosis, malaria, and cancer worldwide. Recently growing concerned over the emergence of the multidrug-resistant fungal pathogen, Candida auris. The fungus has infected people across 59 countries and the mortality rate of the infected person is 60 to 70%. provided that most of the patients are hospitalized and have other medical complications. In the recent Covid19 pandemic, the fungus has caused many outbreaks of C. auris in healthcare facilities. C. auris infections show high drug-resistant characteristics, of which some of them are resistant to the last resort of the antifungal echinocandin class of antibiotics. WHO has published a fungal priority list that needs to address unmet research of C. auris. The prevalence of echinocandin and fluconazole resistance amongst C. auris clinical isolates is challenging as both of them are the most widely administered antifungals because of their broad spectrum of activity as well as low live toxicity as compared to polyene and 5-fluorocytosine. Its calls for finding new targets or a new strategy for delivering drugs into the fungus as well as targets that disrupt fungal cellular functions in the treatment of the rising number of C. auris infections worldwide. There are combination therapies available to treat drug resistance and restore antimicrobial efficacy. Combination therapy has the potential to confer enhanced efficacy and reduce vulnerability to the emergence of drug resistance. In this study, we will try to understand different pathways required for drug sensing and temperature-dependent molecular mechanism for drug tolerance. We have found temperature as a factor for high drug tolerance. At 30˚C the fungus is highly susceptible to drugs but at 37˚C it can tolerate drugs at much higher concentrations. The preliminary data suggest the that calcineurin pathway can re-sensitize the fungus to known antifungal agents. So by addressing this difference we can find out molecules that regulate the expression of different effector molecules which lead to drug tolerance. These molecules can be targeted to make new therapeutic interventions for this highly drug-resistant fungus. Our preliminary unpublished but extremely promising data suggests that using a combination of FDA-approved non-antifungal drugs can re-sensitize the fungus to known antifungal agents. We will also identify the drug-sensing pathway which gets shut off by the combination strategy. Identified, the promising lead compound could be a potential candidate for combination therapy for further development approach to stop key fungal virulence traits and re-sensitize resistant fungal isolates to azoles and caspofungin. Targeting multiple possible drug-resistant pathways can curtail the growth of C. auris.