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

Bacterial cytoplasmic membrane phosphatidylglycerol-rich and cardiolipin-rich domains are specialized lipid microdomains within the inner membrane of bacteria, primarily composed of the anionic phospholipids phosphatidylglycerol (PG) and cardiolipin (CL) (Weibel, 2011) [1.2.5]. These domains are typically localized at high-curvature regions such as the cell poles and the division septum, where they serve as essential scaffolds for organizing proteins involved in cell division, cell wall synthesis, and oxidative phosphorylation (Mingeot-Leclercq et al., 2017) [1.1.1]. Because of their critical role in bacterial physiology and their distinct composition compared to mammalian membranes, they are significant targets for antimicrobial therapy (Liu et al., 2024) [1.4.1]. Drugs like daptomycin exploit these domains by binding to PG in a calcium-dependent manner, causing lipid clustering and membrane depolarization (Taylor & Palmer, 2016) [1.3.3]. Other agents, such as amphiphilic aminoglycosides, target cardiolipin-rich domains to disrupt the respiratory chain and displace cytoskeleton-associated proteins like MreB (Mingeot-Leclercq et al., 2017) [1.2.1]. Resistance to such drugs often involves the remodeling of these domains, such as the conversion of PG to lysyl-PG or the redistribution of CL (Munita et al., 2016) [1.3.2]. Targeting these domains provides a pathway for developing antibiotics against multidrug-resistant pathogens like MRSA and Pseudomonas aeruginosa (Liu et al., 2025) [1.4.2].

Other names

Cardiolipin microdomainsPhosphatidylglycerol-rich domainsAnionic lipid microdomainsBacterial membrane raftsCL-rich domains

Drugs targeting these domains typically bind to anionic phospholipids like phosphatidylglycerol (PG) or cardiolipin (CL) in a concentration-dependent or calcium-dependent manner. For example, daptomycin binds PG to form daptomycin-PG clusters that depolarize the membrane (Taylor & Palmer, 2016) [1.3.3]. Other agents like 3',6-dinonyl neamine induce cardiolipin relocation, which disrupts the respiratory chain and displaces proteins like MreB (Mingeot-Leclercq et al., 2017) [1.1.1]. These interactions lead to the disruption of membrane biophysical properties, dissipation of the proton motive force, and metabolic disturbance, ultimately resulting in cell death (Liu et al., 2024) [1.4.1].