The major emphasis of our laboratory is to understand the molecular and cellular bases of gram-positive bacterial pathogenesis especially related to group A Streptococcus (GAS, S. pyogenes), Streptococcus pneumoniae (pneumococcus), Staphylococcus aureus (S. aureus including multidrug-resistant S. aureus [MRSA]), Enterococcus faecalis/faecium (enterococci), and Clostridiodes diffcile. While in the past our lab has shown how surface proteins and anchorless surface proteins are decorated to perform a variety of virulence-related functions in some of these pathogens, we have now characterized the functional role of a conserved eukaryotic-type serine/ threonine kinase (STK) and phosphatase (STP) in Gram-positive pathogens’ virulence and antimicrobial drug resistance (AMR). Our ongoing efforts are to understand the role of post-translational modification carried out by these and other bacterial tyrosine kinase and phosphatases of these pathogens in virulence and how they exploit host signaling events for their survival within host cells. To that end, we have also identified MRSA-specific small molecule inhibitor (Inh2-B1) that serves as a “two-edged sword” in the form of a “beta-lactam antibiotic resistance breaker” and an “antibiofilm agent.” Similar kinds of studies are underway for C. difficile infection. In collaboration with Clinical microbiology Labs, we are also investigating the mechanism of colistin-resistance in Gram-negative bacteria and cephalosporin resistance in Neisseria gonorrhoeae.
