Dr Bouley’s current research focuses on studying the antibiotic resistance mechanisms of carbapenem-resistant Enterobacteriaceae (CRE). The main focus of this research is on studying L,D-transpeptidases (Ldts), which are enzymes that form specific peptide crosslinks of the bacterial cell wall. These Ldts are structurally distinct from penicillin-binding proteins (PBPs) but carry-out similar enzymatic reactions. These Ldts are not inhibited by the majority of beta-lactam antibiotics (penicillins, cephalosporins, etc) like the PBPs. Thus, when these bacteria are treated with a beta-lactam antibiotic the Ldts are able to continue catalyzing the cross-linking of the cell wall and prevent cell lysis and death. The Bouley lab is focusing on expressing and purifying Ldts found in several CRE strains as well as investigating what beta-lactam antibiotics are able to inhibit these enzymes. X-ray crystallography will be used to determine the structure of these enzymes and structure-based drug design will be utilized to develop novel inhibitors.
