Insights into In Vivo Activities of Lantibiotics from Gallidermin and Epidermin Mode-of-Action Studies
| Autor: | Hans-Georg Sahl, Tanja Schneider, Raquel Regina Bonelli, Imke Wiedemann |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Pharmacology
chemistry.chemical_classification Lipid II biology Molecular Sequence Data Lactococcus lactis Peptide Lantibiotics biology.organism_classification Uridine Diphosphate N-Acetylmuramic Acid Anti-Bacterial Agents Amino acid Cell wall chemistry.chemical_compound Infectious Diseases Bacteriocins Bacteriocin chemistry Biochemistry Pharmacology (medical) Amino Acid Sequence Peptides Mechanisms of Action: Physiological Effects Nisin |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 50:1449-1457 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.50.4.1449-1457.2006 |
| Popis: | The activity of lanthionine-containing peptide antibiotics (lantibiotics) is based on different killing mechanisms which may be combined in one molecule. The prototype lantibiotic nisin inhibits peptidoglycan synthesis and forms pores through specific interaction with the cell wall precursor lipid II. Gallidermin and epidermin possess the same putative lipid II binding motif as nisin; however, both peptides are considerably shorter (22 amino acids, compared to 34 in nisin). We demonstrate that in model membranes, lipid II-mediated pore formation by gallidermin depends on membrane thickness. With intact cells, pore formation was less pronounced than for nisin and occurred only in some strains. InLactococcus lactissubsp.cremorisHP, gallidermin was not able to release K+, and a mutant peptide, [A12L]gallidermin, in which the ability to form pores was disrupted, was as potent as wild-type gallidermin, indicating that pore formation does not contribute to killing. In contrast, nisin rapidly formed pores in theL. lactisstrain; however, it was approximately 10-fold less effective in killing. The superior activity of gallidermin in a cell wall biosynthesis assay may help to explain this high potency. Generally, it appears that the multiple activities of lantibiotics combine differently for individual target strains. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|