title: Antimicrobial Peptides Targeting Gram-Positive Bacteria.
abstract: Antimicrobial peptides (AMPs) have remarkably different structures as well as biological activity profiles, whereupon most of these peptides are supposed to kill bacteria via membrane damage. In order to understand their molecular mechanism and target cell specificity for Gram-positive bacteria, it is essential to consider the architecture of their cell envelopes. Before AMPs can interact with the cytoplasmic membrane of Gram-positive bacteria, they have to traverse the cell wall composed of wall- and lipoteichoic acids and peptidoglycan. While interaction of AMPs with peptidoglycan might rather facilitate penetration, interaction with anionic teichoic acids may act as either a trap for AMPs or a ladder for a route to the cytoplasmic membrane. Interaction with the cytoplasmic membrane frequently leads to lipid segregation affecting membrane domain organization, which affects membrane permeability, inhibits cell division processes or leads to delocalization of essential peripheral membrane proteins. Further, precursors of cell wall components, especially the highly conserved lipid II, are directly targeted by AMPs. Thereby, the peptides do not inhibit peptidoglycan synthesis via binding to proteins like common antibiotics, but form a complex with the precursor molecule, which in addition can promote pore formation and membrane disruption. Thus, the multifaceted mode of actions will make AMPs superior to antibiotics that act only on one specific target.
authors.affiliation: Institute of Molecular Biosciences, Biophysics Division, University of Graz, NAWI Graz, Austria. nermina.malanovic@uni-graz.at.
authors.forename: Nermina
authors.initials: N
authors.lastname: Malanovic
authors.affiliation: Institute of Molecular Biosciences, Biophysics Division, University of Graz, NAWI Graz, Austria. karl.lohner@uni-graz.at.|BioTechMed Graz, Humboldtstrasse 50/III, 8010 Graz, Austria. karl.lohner@uni-graz.at.
authors.forename: Karl
authors.initials: K
authors.lastname: Lohner
keywords: cell wall; lipoteichoic acid; membrane phospholipids; mode of action of AMPs; peptidoglycan biosynthesis