Our research program is focused on the discovery and mechanistic characterization of novel therapeutic strategies to combat multidrug-resistant (MDR) bacterial and fungal pathogens. We emphasize both direct-acting antimicrobial agents and antibiotic adjuvants targeting vancomycin-resistant Gram-positive bacteria and azole-resistant fungi. A central component of our work has involved repurposing disulfiram and designing structurally related analogs as antimicrobial and potentiating agents. In vancomycin intermediate and vancomycin-resistant Staphylococcus aureus (VISA, VSRA), disulfiram functions as an adjuvant that significantly lowers the minimum inhibitory concentration (MIC) of vancomycin, restoring susceptibility to this first-line glycopeptide. Mechanistic investigations in methicillin-resistant S. aureus (MRSA) indicate that disulfiram disrupts central glucose metabolism, suggesting metabolic reprogramming as a driver of impaired cell wall homeostasis and reversal of vancomycin resistance phenotypes.
In fungal pathogens, disulfiram was also found to exhibit intrinsic fungicidal activity against clinically relevant Candida species. Notably, its antifungal efficacy demonstrates copper-dependent synergism, consistent with a metal-mediated mechanism that enhances intracellular stress responses and results in a fungistatic-to-fungicidal transition. These findings position disulfiram as a dual-function antimicrobial scaffold with both redox-active and metal-chelating properties. In parallel, we evaluated structurally related (dithioperoxo)thiolate-based analogs that demonstrated activity against azole-resistant Aspergillus fumigatus and MDR Candida auris, highlighting the potential of this chemotype as a next-generation antifungal platform.
Highlights of our research publications from various lab projects are presented below.
Projects in the lab have been supported by NIH-NIAID, NASA-EPSCoR, WVCTSI, and Marshall University Schools of Pharmacy and Medicine.
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