Membrane-damaging activity of Taiwan cobra cardiotoxin 3 is responsible for its bactericidal activity

Membrane-damaging activity of Taiwan cobra cardiotoxin 3 is responsible for its bactericidal activity
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DOI:
10.1016/j.toxicon.2011.04.021
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发表时间:
2011-07-01
期刊:
影响因子:
2.8
通讯作者:
Chang, Long-Sen
Chang, Long-Sen
中科院分区:
医学4区
文献类型:
--
作者:
Chen, Li-Wen;Kao, Pei-Hsiu;Chang, Long-Sen

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本研究旨在探讨中华眼镜蛇心脏毒素3(CTX 3)的膜损伤活性与杀菌活性之间的因果关系。CTX 3对金黄色葡萄球菌(革兰氏阳性菌)的生长抑制活性高于大肠杆菌(革兰氏阴性菌)。CTX 3的抗菌活性与细菌细胞膜通透性的增加正相关。形态学观察表明,CTX 3破坏了细菌细胞膜的完整性,与脂多糖(LPS)和脂磷壁酸(LTA)具有相似的结合能力,破坏LPS层的稳定性和抑制细胞壁LTA的生物合成增强了CTX 3对大肠杆菌的杀菌作用。杆菌和S.金黄色葡萄球菌。与E. coli,CTX 3对S.金黄色。LPS和LTA可抑制CTX 3的膜损伤活性,而增加CTX 3浓度则可抵消LPS和LTA的抑制作用。CTX 3的环II上的Met残基的氧化同时降低了CTX 3的膜透化活性和杀菌作用。总之,我们的数据表明,CTX 3杀菌活性高度依赖于其诱导膜渗透性的能力。(C)2011爱思唯尔有限公司保留所有权利。
This study investigates the causal relationship between membrane-damaging activity and bactericidal activity of Naja naja atra (Taiwan cobra) cardiotoxin 3 (CTX3). CTX3 showed greater inhibitory activity for the growth of Staphylococcus aureus (Gram-positive bacteria) relative to that of Escherichia coli (Gram-negative bacteria). The CTX3 antibacterial activity is positively correlated with the increase in membrane permeability of bacterial cells. Morphological examination showed that CTX3 disrupted bacterial membrane integrity.CTX3 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 the CTX3 bactericidal effect on E. coli. and S. aureus, respectively. Compared with that of E. coli, CTX3 notably permeabilized model membrane of S. aureus. CTX3 membrane-damaging activity was inhibited by LPS and LTA, while increasing the CTX3 concentration counteracted the inhibitory action of LPS and LTA. Oxidation of Met residues on loop II of CTX3 simultaneously reduced the membrane-permeabilizing activity and bactericidal effect of CTX3. Taken together, our data indicate that CTX3 bactericidal activity depends highly on its ability to induce membrane permeability. (C) 2011 Elsevier Ltd. All rights reserved.