Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II.
Defensins constitute a major class of cationic antimicrobial peptides in mammals and vertebrates, acting as effectors of innate immunity against infectious microorganisms. It is generally accepted that defensins are bactericidal by disrupting the anionic microbial membrane. Here, we provide evidence that membrane activity of human alpha-defensins does not correlate with antibacterial killing. We further show that the alpha-defensin human neutrophil peptide-1 (HNP1) binds to the cell wall precursor lipid II and that reduction of lipid II levels in the bacterial membrane significantly reduces bacterial killing. The interaction between defensins and lipid II suggests the inhibition of cell wall synthesis as a novel antibacterial mechanism of this important class of host defense peptides.
de Leeuw
Erik
E
University of Maryland Baltimore School of Medicine, Institute of Human Virology, Department of Biochemistry and Molecular Biology, Baltimore, MD 21201, USA. edeleeuw2@ihv.umaryland.edu
Li
Changqing
C
Zeng
Pengyun
P
Li
Chong
C
Diepeveen-de Buin
Marlies
M
Lu
Wei-Yue
WY
Breukink
Eefjan
E
Lu
Wuyuan
W
D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D011485:Protein Binding; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism* / Q000494:pharmacology
D008563:Membrane Lipids; D014538:Uridine Diphosphate N-Acetylmuramic Acid; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol