Bacterial cytoplasmic membrane (phosphatidylglycerol-enriched)

The bacterial cytoplasmic membrane is a phospholipid bilayer that serves as the primary barrier and metabolic hub for bacterial cells. In many bacteria, particularly Gram-positive species, this membrane is heavily enriched with phosphatidylglycerol (PG), an anionic phospholipid that imparts a significant negative surface charge [1.1.5, 1.4.2]. This negative charge is a key physiological feature that allows for the selective targeting of bacteria by cationic antimicrobial peptides and lipopeptide antibiotics like daptomycin [1.1.4, 1.2.4]. Daptomycin specifically interacts with PG in a calcium-dependent manner, leading to its insertion into the membrane, oligomerization, and subsequent membrane depolarization [1.3.1, 1.3.4]. This disruption of the membrane potential and the resulting leakage of intracellular ions, such as potassium, ultimately leads to rapid bacterial cell death [1.3.3]. Beyond its role in drug interaction, the PG-enriched membrane is vital for maintaining the proton motive force required for ATP synthesis and for anchoring proteins involved in cell wall synthesis and division [1.4.3, 1.4.4]. Bacteria can develop resistance to membrane-targeting drugs by modifying PG into lysyl-phosphatidylglycerol, which reduces the net negative charge and decreases drug affinity [1.2.3, 1.2.5]. Consequently, the composition and integrity of the bacterial cytoplasmic membrane are central to both bacterial survival and the efficacy of several classes of life-saving antibiotics [1.1.1, 1.1.3].

Other names

Bacterial inner membraneAnionic bacterial membranePG-rich bacterial membraneBacterial plasma membrane

Antibacterial agents target the anionic phosphatidylglycerol headgroups, often requiring calcium ions for binding, which facilitates insertion into the lipid bilayer, oligomerization, and subsequent membrane depolarization or pore formation [1.1.4, 1.3.1, 1.3.4].