Detergent-like activity and alpha-helical structure of warnericin RK, an anti-Legionella peptide.
Warnericin RK is the first antimicrobial peptide known to be active against Legionella pneumophila, a pathogen bacterium that is responsible for severe pneumonia. Strikingly, this peptide displays a very narrow range of antimicrobial activity, almost limited to the Legionella genus, and a hemolytic activity. A similar activity has been described for delta-lysin, a well-known hemolytic peptide of Staphylococci that has not been described as antimicrobial. In this study we aimed to understand the mode of action of warnericin RK and to explain its particular target specificity. We found that warnericin RK permeabilizes artificial membranes in a voltage-independent manner. Osmotic protection experiments on erythrocytes showed that warnericin RK does not form well-defined pores, suggesting a detergent-like mode of action, as previously described for delta-lysin at high concentrations. Warnericin RK also permeabilized Legionella cells, and these cells displayed a high sensitivity to detergents. Depending on the detergent used, Legionella was from 10- to 1000-fold more sensitive than the other bacteria tested. Finally, the structure of warnericin RK was investigated by means of circular dichroism and NMR spectroscopy. The peptide adopted an amphiphilic alpha-helical structure, consistent with the proposed mode of action. We conclude that the specificity of warnericin RK toward Legionella results from both the detergent-like mode of action of the peptide and the high sensitivity of these bacteria to detergents.
Verdon
Julien
J
Laboratoire de Chimie et Microbiologie de l'Eau, Unite Mixte de Recherche, Centre National de la Recherche Scientifique 6008, Université de Poitiers, Poitiers, France.
Falge
Mirjam
M
Maier
Elke
E
Bruhn
Heike
H
Steinert
Michael
M
Faber
Cornelius
C
Benz
Roland
R
Héchard
Yann
Y
D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002942:Circular Dichroism; D003902:Detergents / Q000494:pharmacology*; D004553:Electric Conductivity; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D007875:Legionella / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008051:Lipid Bilayers / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008567:Membranes, Artificial; D009995:Osmosis; D010539:Permeability; D017433:Protein Structure, Secondary; D013379:Substrate Specificity
D023181:Antimicrobial Cationic Peptides; D003902:Detergents; D007473:Ion Channels; D008051:Lipid Bilayers; D008567:Membranes, Artificial