Therapeutic compounds targeting Lipid II for antibacterial purposes

Resistance against commonly used antibiotics has emerged in all bacterial pathogens. In fact, there is no antibiotic currently in clinical use against which resistance has not been reported. In particular, rapidly increasing urbanization in developing nations are sites of major concern. Additionally, the widespread practice by physicians to prescribe antibiotics in cases of viral infections puts selective pressure on antibiotics that still remain effective and it will only be a matter of time before resistance develops on a large scale. The biosynthesis pathway of the bacterial cell wall is well studied and a validated target for the development of antibacterial agents. Cell wall biosynthesis involves two major processes; 1) the biosynthesis of cell wall teichoic acids and 2) the biosynthesis of peptidoglycan. Key molecules in these pathways, including enzymes and precursor molecules are attractive targets for the development of novel antibacterial agents. In this review, we will focus on the major class of natural antibacterial compounds that target the peptidoglycan precursor molecule Lipid II; namely the glycopeptides, including the novel generation of lipoglycopeptides. We will discuss their mechanism-of-action and clinical applications. Further, we will briefly discuss additional peptides that target Lipid II such as the lantibiotic nisin and defensins. We will highlight recent developments and future perspectives.