Glycopeptide and lipoglycopeptide antibiotics

Today, the frequency of resistance to glycopeptide antibiotics represents a serious threat to public health. Thus, research into the molecular basis for glycopeptide resistance aims to design new glycopeptide antibiotics with activity against both sensitive and resistant bacterial strains. Against this background, this review describes the structures of a set of important natural glycopeptide antibiotics and outlines their biosynthetic pathways. It discusses what is known about the mode of action of the glycopeptides and how structural differences influence biological activity. Furthermore, it illustrates how resistance to the glycopeptides develops and summarizes efforts to develop glycopeptides that can overcome resistance. Finally, it outlines how access to unnatural glycopeptide has provided tools to identify new targets of the glycopeptide class and activity differences observed for natural glycopeptides against different bacterial pathogens.