Small cationic antimicrobial peptides delocalize peripheral membrane proteins.
Short antimicrobial peptides rich in arginine (R) and tryptophan (W) interact with membranes. To learn how this interaction leads to bacterial death, we characterized the effects of the minimal pharmacophore RWRWRW-NH2. A ruthenium-substituted derivative of this peptide localized to the membrane in vivo, and the peptide also integrated readily into mixed phospholipid bilayers that resemble Gram-positive membranes. Proteome and Western blot analyses showed that integration of the peptide caused delocalization of peripheral membrane proteins essential for respiration and cell-wall biosynthesis, limiting cellular energy and undermining cell-wall integrity. This delocalization phenomenon also was observed with the cyclic peptide gramicidin S, indicating the generality of the mechanism. Exogenous glutamate increases tolerance to the peptide, indicating that osmotic destabilization also contributes to antibacterial efficacy. Bacillus subtilis responds to peptide stress by releasing osmoprotective amino acids, in part via mechanosensitive channels. This response is triggered by membrane-targeting bacteriolytic peptides of different structural classes as well as by hypoosmotic conditions.
Biology of Microorganisms, Bioinorganic Chemistry, and Plant Physiology, Immune Proteomics, Medical Proteome Center, and Institute of Physiological Chemistry, Ruhr University Bochum, 44801 Bochum, Germany.
Michaela
M
Wenzel
Alina Iulia
AI
Chiriac
Andreas
A
Otto
Dagmar
D
Zweytick
Caroline
C
May
Catherine
C
Schumacher
Ronald
R
Gust
H Bauke
HB
Albada
Maya
M
Penkova
Ute
U
Krämer
Ralf
R
Erdmann
Nils
N
Metzler-Nolte
Suzana K
SK
Straus
Erhard
E
Bremer
Dörte
D
Becher
Heike
H
Brötz-Oesterhelt
Hans-Georg
HG
Sahl
Julia Elisabeth
JE
Bandow
D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001412:Bacillus subtilis / Q000378:metabolism; D001665:Binding Sites; D045304:Cytochromes c / Q000378:metabolism; D006706:Homeostasis; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008565:Membrane Proteins; D010743:Phospholipids; D045304:Cytochromes c
hypoosmotic stress response; mechanism of action; metallocenes; respiratory chain