The bacterial cell wall as a source of antibacterial targets

Expert Opinion on Therapeutic Targets
David W Green

Abstract

This review focuses on target-based approaches for developing new chemical classes of antibacterial agents aimed at the bacterial cell wall. The clinical success of antibiotics such as beta-lactams and glycopeptides validates this chemotherapeutic strategy and emerging resistance to these agents warrants the development of new antibacterial drugs. Understanding the mechanism of action and resistance to beta-lactams and glycopeptides at a molecular level has supported the development of new agents that prevent transpeptidation and transglycosylation reactions of peptidoglycan polymerisation. The enzymes involved in the synthesis of the peptidoglycan structural unit have also been targeted for antibacterial discovery. The influence of bacterial genetics and genomics, structural biology, assay development and the properties of known inhibitors on these approaches will be discussed in the context of drug discovery.

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