Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II

Leeuw, Erik de; Li, Changqing; Zeng, Pengyun; Li, Chong; Buin, Marlies Diepeveen-de; Lu, Wei-Yue; Breukink, Eefjan; Lu, Wuyuan

doi:10.1016/j.febslet.2010.03.004

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Volume 584, Issue 8 , Pages 1543-1548, 16 April 2010

Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II

Edited by Renee Tsolis

Erik de Leeuw
- University of Maryland Baltimore School of Medicine, Institute of Human Virology and Department of Biochemistry and Molecular Biology, 725 West Lombard Street, Baltimore, MD 21201, USA
- Corresponding author. Fax: +1 410 706 7583.
Changqing Li
- University of Maryland Baltimore School of Medicine, Institute of Human Virology and Department of Biochemistry and Molecular Biology, 725 West Lombard Street, Baltimore, MD 21201, USA
Pengyun Zeng
- Fudan University School of Pharmacy, Shanghai, China
Chong Li
- Fudan University School of Pharmacy, Shanghai, China
Marlies Diepeveen-de Buin
- Utrecht University, Department of Biochemistry of Membranes, Bijvoet Center for Biomolecular Research, Padualaan 8, 3585 CH, Utrecht, The Netherlands
Wei-Yue Lu
- Fudan University School of Pharmacy, Shanghai, China
Eefjan Breukink
- Utrecht University, Department of Biochemistry of Membranes, Bijvoet Center for Biomolecular Research, Padualaan 8, 3585 CH, Utrecht, The Netherlands
Wuyuan Lu
- University of Maryland Baltimore School of Medicine, Institute of Human Virology and Department of Biochemistry and Molecular Biology, 725 West Lombard Street, Baltimore, MD 21201, USA
- Corresponding author. Fax: +1 410 706 7583.

Received 11 January 2010; received in revised form 1 March 2010; accepted 2 March 2010. published online 08 March 2010.

Abstract

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 α-defensins does not correlate with antibacterial killing. We further show that the α-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.

Keywords: Human neutrophil peptide-1, Defensin, Lipid II