Gram-negative bacterial cytoplasmic membrane lipids

The cytoplasmic or inner membrane (IM) of Gram-negative bacteria is a phospholipid bilayer essential for maintaining the cell's structural integrity and electrochemical gradient [1]. It is primarily composed of phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL), which facilitate vital processes such as ATP synthesis, protein secretion, and lipid biosynthesis [2]. Unlike the outer membrane, the IM lacks lipopolysaccharides but is the site of action for several classes of antibiotics that must first traverse the cell wall [3]. Drugs like polymyxins (e.g., Colistin) and various antimicrobial peptides (AMPs) target these lipids, particularly the anionic PG and CL, to cause membrane depolarization and pore formation [4]. This disruption leads to the leakage of essential ions and metabolites, ultimately resulting in rapid bacterial cell death [5]. Targeting the IM is a key strategy against multi-drug resistant (MDR) pathogens, though the similarity between certain bacterial and mammalian lipids can lead to host toxicity, such as nephrotoxicity [6]. Sources: [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4262121/; [2] https://www.uniprot.org/locations/SL-0038; [3] https://pubmed.ncbi.nlm.nih.gov/27317921/; [4] https://pubchem.ncbi.nlm.nih.gov/compound/Colistin; [5] https://www.nature.com/articles/s41598-017-12703-6; [6] https://www.ncbi.nlm.nih.gov/books/NBK557777/.

Other names

Gram-negative bacterial inner membrane lipidsBacterial cytoplasmic membrane phospholipidsInner membrane phospholipidsGram-negative bacterial IM lipids

Drugs targeting these lipids typically act by binding to anionic phospholipids (such as phosphatidylglycerol and cardiolipin), leading to membrane depolarization, pore formation, and physical disruption of the lipid bilayer, which results in the leakage of intracellular contents and rapid cell death.