Detergent-Like Activity and α-Helical Structure of Warnericin RK, an Anti-Legionella Peptide

Abstract

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.

Anthrax toxin-induced rupture of artificial lipid bilayer membranes

“…For example, warnericin RK acts like a detergent that permeabilizes Legionella membranes. 102 In DiPhyPC membranes, the polypeptide behaves like poorly defined ion channels at low potentials. At potentials >60 mV, an erratic conductance leads to membrane rupture, as we observed here with anthrax toxin (e.g., Figs.…”

“…In those cases, osmoticants and lysosomotropic agents draw water into the endosome, causing it to swell and burst. 116 In addition, various naturally occurring 102,117,118 and designer peptides 119,120 use a detergent-like action to solubilize, destabilize, and rupture membranes. …”

Alpha-helical cationic antimicrobial peptides: relationships of structure and function

“…Antimicrobial peptides (AMPs) represent such a new class of antibiotics. Many researchers have contributed to the understanding of the structure-activity relationship of AMPs (Ali et al, 2009;Joanne et al, 2009;Manna and Mukhopadhyay, 2009;Resende et al, 2009;Verdon et al, 2009). Traditional antibiotics generally target a particular physiological process of bacteria, such as cell wall synthesis, DNA replication etc.…”

Characterization and purification of bacteriocin produced by Enterococcus sp. GHB26 isolated from Algerian paste of dates Ghars

“…Using nisin as a standard, its elution was recorded to a retention time of 26 min. Verdon (2009) showed that the bacteriocins that have the same size and the same hydrophobicity properties will elute by RP-HPLC at very near time; this is the case of the bacteriocin GHB26 (23.99 min) and nisin (26 min).…”