Bacterial phosphatidylglycerol- and cardiolipin-rich membrane domains (PG/CL-rich domains)

Bacterial phosphatidylglycerol (PG)- and cardiolipin (CL)-rich membrane domains are specialized, highly organized regions within the bacterial cytoplasmic membrane characterized by a high density of anionic phospholipids. Often termed functional membrane microdomains (FMMs) or bacterial lipid rafts, these areas serve as essential scaffolds for organizing various physiological processes, including cell wall biosynthesis, protein secretion, and signal transduction (Lopez & Kolter, 2010, Genes & Development). By providing a distinct physicochemical environment, these domains recruit and stabilize specific protein complexes, such as the divisome and the Sec secretion machinery (Strahl et al., 2014, Frontiers in Microbiology). In clinical medicine, these domains are critical targets for several potent antibiotics. For instance, the lipopeptide daptomycin specifically targets PG-rich regions to induce membrane depolarization, while polymyxins interact with anionic lipids to disrupt the integrity of the bacterial envelope (Epand & Epand, 2009, BBA - Biomembranes). Because the high concentration of anionic lipids in these domains is a hallmark of bacterial membranes compared to the zwitterionic-rich outer leaflets of mammalian cells, they provide a basis for selective antimicrobial action, though potential interference with host mitochondrial membranes remains a therapeutic challenge.

Other names

Functional membrane microdomains (FMMs)Bacterial lipid raftsAnionic lipid domainsCardiolipin-rich domainsPhosphatidylglycerol-rich domainsBacterial membrane microdomains

Drugs targeting these domains typically act through membrane depolarization, pore formation, or the disruption of membrane-associated protein complexes. For example, daptomycin binds to phosphatidylglycerol-rich regions in a calcium-dependent manner, leading to the formation of complexes that cause potassium efflux and membrane dysfunction (Müller et al., 2016, PNAS). Other agents may sequester essential lipid-linked precursors like Lipid II within these domains, thereby inhibiting cell wall biosynthesis (Epand & Epand, 2009, BBA - Biomembranes).