University of Maryland Baltimore School of Medicine, Institute of Human Virology, Department of Biochemistry and Molecular Biology, Baltimore, MD 21201, USA.
FEBS Lett. 2010 Apr 16;584(8):1543-8. doi: 10.1016/j.febslet.2010.03.004. Epub 2010 Mar 7.
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.
防御素是哺乳动物和脊椎动物中一类主要的阳离子抗菌肽，作为先天免疫抵抗感染微生物的效应分子。人们普遍认为，防御素通过破坏带负电荷的微生物膜而具有杀菌作用。在这里，我们提供的证据表明，人α-防御素的膜活性与抗菌杀菌作用无关。我们还进一步表明，人中性粒细胞肽-1（HNP1）与细胞壁前体脂质 II 结合，并且细菌膜中脂质 II 水平的降低显著降低了细菌的杀菌作用。防御素与脂质 II 的相互作用提示细胞壁合成的抑制可能是宿主防御肽这一重要家族的新型抗菌机制。
