Research Projects

Antimicrobial resistance (AMR) is a growing global public health concern, with multi-drug-resistant bacteria causing over 700,000 fatalities annually and predicted to cause over ten million deaths by 2050. Vibrio sp., a type of bacteria, is being hydrolyzed by various antibiotic resistant mechanisms, leading to cholera-like epidemics. A recent report by Lin et al. identified a putative antibiotic resistance regulon (var) in Vibrio Cholerae, which contains a transcription regulator, VarR, transcribed close to resistance genes, metallo-beta-lactamase (VarG), and an antibiotic efflux pump (VarABCDEF). The study hypothesizes that characterization of these targets is crucial for understanding the molecular mechanism of antibiotic recognition and resistance due to var regulon specific to Vibrio sp. Combining invitro and insilico approaches in the development of structure-based inhibitors might increase antibiotic sensitivity in Vibrio strains. The proposal involves structural and biochemical characterization of VarR, a transcriptional regulator for var regulon, and VarG, a metallo-beta-lactamase enzyme. The aim is to determine the crystal structures of VarG and VarR in V. cholerae and V. vulnificus using X-ray crystallography and perform in vitro biochemical characterization and insilico structure-based drug design for their inhibition. The proposed study aims to isolate the soluble protein fraction of the identified protein targets, determine crystal structure apo- and holo-enzymes for both VarG and VarR, understand the molecular mechanism of substrate recognition and effect on the downstream pathway, screen and identify inhibitor drug molecules insilico, and perform invitro inhibitor binding studies.