Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
Peptides. 2011 Aug;32(8):1755-63. doi: 10.1016/j.peptides.2011.06.026. Epub 2011 Jul 5.
The aim of the present study is to investigate the causal relationship between membrane-damaging activity and bactericidal activity of Naja nigricollis toxin γ. Toxin γ showed a similar inhibitory activity on the growth of Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria). Antibacterial activity of toxin γ correlated positively with increase in membrane permeability of bacterial cells. Morphological examination showed that toxin γ disrupted the integrity of bacterial membrane. Toxin γ showed similar binding capability with lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and destabilization of LPS layer and inhibition of LTA biosynthesis on cell wall increased bactericidal effect of toxin γ on E. coli and S. aureus, respectively. Although the potency of toxin γ on permeabilizing model membrane of E. coli and S. aureus was similar, the mode of interaction between toxin γ and model membrane of E. coli and S. aureus differed. Membrane-damaging activity of toxin γ was inhibited by either LPS or LTA. Nevertheless, LPS and LTA altered differently membrane-bound conformation of toxin γ. Taken together, our data suggest that bactericidal activity of toxin γ depends on its ability to induce membrane permeability, and that LPS and LTA structurally suppresses bactericidal effect of toxin γ.
本研究旨在探讨眼镜蛇毒素 γ 的膜损伤活性与杀菌活性之间的因果关系。毒素 γ 对金黄色葡萄球菌(革兰氏阳性菌)和大肠杆菌(革兰氏阴性菌)的生长具有相似的抑制活性。毒素 γ 的杀菌活性与细菌细胞膜通透性的增加呈正相关。形态学检查表明,毒素 γ 破坏了细菌膜的完整性。毒素 γ 与脂多糖 (LPS) 和脂磷壁酸 (LTA) 具有相似的结合能力,并且 LPS 层的不稳定性和细胞壁上 LTA 生物合成的抑制分别增加了毒素 γ 对大肠杆菌和金黄色葡萄球菌的杀菌作用。尽管毒素 γ 对大肠杆菌和金黄色葡萄球菌模型膜的通透性具有相似的效力,但毒素 γ 与大肠杆菌和金黄色葡萄球菌模型膜之间的相互作用模式不同。毒素 γ 的膜损伤活性受到 LPS 或 LTA 的抑制。然而,LPS 和 LTA 以不同的方式改变了毒素 γ 的膜结合构象。综上所述,我们的数据表明,毒素 γ 的杀菌活性取决于其诱导膜通透性的能力,并且 LPS 和 LTA 在结构上抑制了毒素 γ 的杀菌作用。