The cell wall, composed mostly of peptidoglycan and teichoic acid, allows passage of essential metal ions and nutrients while protecting against attack by antimicrobial agents. The influence of metals on bacterial virulence is well established, however quantitative models for metal binding in the cell wall of Gram-positive bacteria, such as Staphylococcus aureus, do not exist. We have described NMR studies of metal ion binding to teichoic acid and used quantum mechanical calculations to provide precise structural information.
Current projects are a direct logical extension of information gained from studying metal chelation in the bacterial cell wall. These data led us to consider the biochemical structures as the basis for new approaches to kill bacterial pathogens. Gram-positive bacteria use anionic teichoic acid to chelate metals and we have been able to block this process with cationic polymers that displace metal ions from the teichoic acid sites. This led to the discovery that branched poly(ethylenimine) restores β-lactam antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA). We have protected our invention with a patent.
Research keywords: MRSA, antibiotics, beta-lactams, drug development