Lipid II as a Target for Novel Antibiotics: Structural and Molecular Dynamics Studies

Abstract

The growing problem of antibiotic resistance in medicine is focusing attention on antimicrobial compounds targeting non-protein molecules, which have more conserved structures compared to proteins or peptides. One of the most promising and studied targets is lipid II—the bacterial cell wall biosynthetic pathway principal compound. Lipid II is unique for the bacterial membrane only and has a conserved chemical structure. There are several classes of natural antibiotics targeting lipid II, some of which block peptidoglycan synthesis by formation of a strong complex with lipid II; others have an additional bactericidal mechanism involving disruption of the membrane integrity. This review examines the prospects of using such antibacterial substances as new drugs to combat antibiotic-resistant pathogens. The main emphasis is on the studies of the membrane-embedded lipid II structure and how water-soluble antibiotics recognize its molecular structure, as well as on computer modeling of their interaction.