Cardiolipin-rich and lipid II-associated membrane microdomain (CL-Lipid II microdomain)

Cardiolipin-rich and lipid II-associated membrane microdomains are specialized, functional regions within the bacterial plasma membrane, primarily characterized in Gram-positive species such as Staphylococcus aureus and Bacillus subtilis. These domains act as organizational scaffolds that co-localize lipid II, a vital precursor for peptidoglycan synthesis, with cardiolipin, a phospholipid that aids in the recruitment and stabilization of membrane-associated proteins involved in cell wall assembly and division (Müller et al., 2016, Science). By concentrating these essential components, the microdomains facilitate efficient bacterial growth and maintain structural integrity. These domains are a critical therapeutic target for the lipopeptide antibiotic daptomycin, which requires both cardiolipin and lipid II for optimal binding and membrane insertion (Grein et al., 2020, Nature Communications). Interaction with these domains leads to the displacement of peripheral membrane proteins like MurG and DivIVA, resulting in the catastrophic failure of cell wall synthesis and rapid bacterial cell death through membrane depolarization.

Other names

Bacterial lipid raftsFunctional membrane microdomains (FMMs)Cardiolipin-rich domainsLipid II-containing microdomains

Antibiotics like daptomycin bind to these microdomains in a calcium-dependent manner, causing the displacement of essential cell wall synthesis proteins and inducing membrane depolarization or pore formation.