Bacterial cell membrane and cell wall lipid domains (FMM)

Bacterial cell membrane and cell wall lipid domains, frequently termed functional membrane microdomains (FMMs), are specialized, highly ordered regions within the bacterial envelope that organize essential physiological processes (Lopez & Kolter, 2010). These domains are enriched in specific lipids, such as polyisoprenoids or hopanoids, and serve as assembly platforms for protein complexes involved in cell wall synthesis, protein secretion, and signal transduction (Bramkamp & Lopez, 2015). In many species, these domains are organized by flotillin-like proteins that facilitate the clustering of enzymes like penicillin-binding proteins (PBPs) and the Sec secretion machinery (Strahl et al., 2014). These structures are prime targets for several classes of antibiotics; for instance, daptomycin targets phosphatidylglycerol-rich domains to cause rapid membrane depolarization and cell death (Müller et al., 2016). Additionally, the cell wall precursor Lipid II is often localized within or near these domains, making them central to the action of glycopeptides and lantibiotics (Schneider et al., 2010). Targeting these domains is a key strategy in treating multidrug-resistant infections, as they are vital for maintaining bacterial structural integrity and virulence. However, therapeutic development must carefully manage potential toxicity arising from similarities between bacterial and mammalian membrane components (Zasloff, 2002).

Other names

Functional membrane microdomainsBacterial lipid raftsMembrane microdomainsLipid domainsFluid microdomainsMembrane rafts

Disruption of membrane integrity, induction of membrane depolarization, and inhibition of cell wall synthesis through binding to lipid-linked precursors like Lipid II or specific phospholipids like phosphatidylglycerol.