Binding of an antimicrobial peptide to bacterial cells: Interaction with different species, strains and cellular components.

摘要: Antimicrobial peptides (AMPs) selectively kill bacteria by disrupting their cell membranes, and are promising compounds to fight drug-resistant microbes. Biophysical studies on model membranes have characterized AMP/membrane interactions the mechanism of bilayer perturbation, showing that accumulation cationic peptide molecules in external leaflet leads formation pores ("carpet" mechanism). However, similar quantitative real cells extremely limited. Here, we investigated interaction dansylated PMAP23 (DNS-PMAP23) with a Gram-positive bacterium, 107 bound per needed it. This result is consistent our previous finding for Gram-negative strains, where high threshold killing was determined, demonstrating general relevance carpet bacteria. case strain, this number even exceeds total surface available bacterial membrane. The affinity DNS-PMAP23 anionic teichoic acids wall, but not lipopolysaccharides bacteria, provides rationale finding. To better define role lipids peptide/cell association, studied E. coli mutant strains lacking phosphatidylglycerol and/or cardiolipin. Surprisingly, these showed wild type. rationalized observing an increased content other lipids, thus maintaining membrane charge essentially constant. Finally, association dead order magnitude higher compared live cells, suggesting strong binding intracellular components become accessible after perturbation. effect could play population resistance AMP action, since protect surviving sequestering significant amounts molecules. Overall, data indicate can lead understanding action AMPs.