The bacterial cell envelope is critically relevant to human health. Not only is the cell envelope the interface used by bacteria to interact with their environment (such as the human host), but it also remains one of our best targets for antibiotics. While the biosynthetic enzymes responsible for building the cell envelope have been well characterized, we know very little about the factors involved in controlling cell envelope production and homeostasis. In the Hummels lab, we use a combination of genetics, biochemistry, and cell biology to investigate the regulation of cell envelope biosynthesis and maintenance in Pseudomonas aeruginosa, which is infamous for antibiotic resistance. By better understanding the players involved in these essential processes, we hope to identify new targets for therapeutic development.

Coordination of outer membrane and cell wall biosynthesis. Gram-negative bacteria, such as P. aeruginosa, are characterized by a multi-layered cell envelope consisting of an inner membrane, a cell wall made up of peptidoglycan (PG), and an asymmetric outer membrane with lipopolysaccharide (LPS) comprising the outer leaflet. Both the LPS and PG biosynthetic pathways utilize the essential cell envelope precursor UDP-GlcNAc, but how it is appropriately partitioned to support optimal cell envelope expansion is poorly understood. A major focus in the Hummels lab is to investigate the regulatory strategies involved in balancing use of UDP-GlcNAc between the competing but essential LPS and PG metabolic pathways