Open AccessInsights into In Vivo Activities of Lantibiotics from Gallidermin and Epidermin Mode-of-Action Studies
Author(s) -
Raquel Regina Bonelli,
Tanja Schneider,
HansGeorg Sahl,
Imke Wiedemann
Publication year - 2006
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.50.4.1449-1457.2006
Subject(s) - lantibiotics , nisin , lipid ii , lactococcus lactis , lanthionine , bacteriocin , biochemistry , peptide , peptidoglycan , cell wall , mutant , biology , chemistry , biosynthesis , bacterial cell structure , bacteria , microbiology and biotechnology , antimicrobial , enzyme , gene , lactic acid , genetics
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 lactis subsp.cremoris HP, 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. lactis strain; 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.