Biography

Bacterial cell wall biosynthesis and related antibacterial agents. Our primary research focus is in the area of antibacterial agents targeting bacterial cell wall biosynthesis, the enzyme targets of these agents, the identification and development of new agents targeting this pathway, and the characterization of resistance to such agents. One of our key strengths is in the area of analytical biochemistry, and we have developed widely used and innovative assays for the penicillin-binding proteins (PBPs), including PBP2a from MRSA and other high-molecular mass PBPs – which are particularly challenging enzymes. We have also developed stereospecific, sensitive and precise LC-MS/MS methods for bacterial cell wall metabolites, such as L-Ala, D-Ala, and D-Ala-D-Ala, which enables the in vivo characterization of agents targeting this metabolic pathway, and resistance mechanisms (e.g. vancomycin resistance) which circumvent this pathway. This effort has been extended to the UDP-linked intermediates in the bacterial cell wall biosynthesis pathway, which provides an unprecedented ability to rapidly profile the effect of cell wall biosynthesis inhibitors on the key metabolites in this pathway. We have also identified D-boroAla as an antibacterial agent that targets D-Ala-D-Ala ligase in the bacterial cell wall biosynthesis pathway.

Biological applications of LC-MS/MS technology. Dr. Gutheil established and oversees the Drug Discovery and Metabolomics LC-MS/MS shared instrumentation resource in the School of Pharmacy. This facility currently houses two AB Sciex QTrap LC-MS/MS instruments, and a Biomek 3000 liquid handling workstation. Faculty and graduate students in the School of Pharmacy and other UMKC units are provided training and hands on access to these instruments for use in small to medium sized molecule research. This facility is heavily used and very productive. Efforts to enhance this resource are ongoing.