Structural and functional studies of microbial O-glycosyltransferases that synthesize virulence factors

National Institute Of Dental & Craniofacial Research

Investigators

Abstract

CPS form a dense layer around various strains of pathogenic bacteria. The CPS layer can promote host cell entry by hiding other virulence factors on the bacterial surface that adhere to host cells and also facilitates host immune evasion. Thus, CPS can increase the pathogenicity of bacteria. We are particularly interested in understanding the mechanisms of CPS biosynthesis in bacterial species that are increasingly becoming resistant to antibiotics. To that end, we are using structural and biochemical approaches to study microbial glycosyltransferases (GTs) that synthesize CPS. We are currently attempting to express and purify putative enzymes involved in CPS biosynthesis. Most of our efforts are focused on optimizing the expression and purification protocol of enzymes that are prone to aggregation and degradation. We recently made significant progress in solving these issues and have obtained promising preliminary Cryo-EM data.