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甘露糖基化牛血清白蛋白的抗菌及膜损伤活性

Antibacterial and membrane-damaging activities of mannosylated bovine serum albumin.

作者信息

Tsai Chia-Yu, Chen Ying-Jung, Fu Yaw-Syan, Chang Long-Sen

机构信息

Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.

Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

出版信息

Arch Biochem Biophys. 2015 May 1;573:14-22. doi: 10.1016/j.abb.2015.02.034. Epub 2015 Mar 6.

Abstract

The aim of this study was to test whether mannosylated BSA (Man-BSA) exerts antibacterial activity on Escherichia coli (gram-negative bacteria) and Staphylococcus aureus (gram-positive bacteria) via its membrane-damaging effect. Man-BSA caused inhibition of growth of E. coli and S. aureus. Moreover, bactericidal action of Man-BSA on E. coli and S. aureus positively correlated with the increase in membrane permeability of the bacterial cells. Morphological examination showed that Man-BSA disrupted bacterial membrane integrity. Destabilization of the lipopolysaccharide (LPS) layer and inhibition of lipoteichoic acid (LTA) biosynthesis in the cell wall increased the bactericidal effect of Man-BSA on E. coli and S. aureus. Man-BSA also induced leakage and fusion of membrane-mimicking liposomes in E. coli and S. aureus. Man-BSA showed similar binding affinity for LPS and LTA. LPS and LTA strongly suppressed the membrane-damaging activity of Man-BSA, whereas an increase in the Man-BSA concentration attenuated the inhibitory action of LPS and LTA. Taken together, our data indicate that Man-BSA's bactericidal activity depends strongly on its ability to induce membrane permeability. Moreover, the bactericidal action of Man-BSA proven in this study suggests that Man-BSA may serve as a prototype for the development of anti-infective agents targeting E. coli and S. aureus.

摘要

本研究的目的是测试甘露糖基化牛血清白蛋白(Man-BSA)是否通过其膜损伤作用对大肠杆菌(革兰氏阴性菌)和金黄色葡萄球菌(革兰氏阳性菌)发挥抗菌活性。Man-BSA对大肠杆菌和金黄色葡萄球菌的生长具有抑制作用。此外,Man-BSA对大肠杆菌和金黄色葡萄球菌的杀菌作用与细菌细胞膜通透性的增加呈正相关。形态学检查表明,Man-BSA破坏了细菌膜的完整性。脂多糖(LPS)层的不稳定和细胞壁中脂磷壁酸(LTA)生物合成的抑制增强了Man-BSA对大肠杆菌和金黄色葡萄球菌的杀菌作用。Man-BSA还诱导了大肠杆菌和金黄色葡萄球菌中模拟膜的脂质体的泄漏和融合。Man-BSA对LPS和LTA表现出相似的结合亲和力。LPS和LTA强烈抑制Man-BSA的膜损伤活性,而Man-BSA浓度的增加减弱了LPS和LTA的抑制作用。综上所述,我们的数据表明,Man-BSA的杀菌活性强烈依赖于其诱导膜通透性的能力。此外,本研究中证实的Man-BSA的杀菌作用表明,Man-BSA可能作为开发针对大肠杆菌和金黄色葡萄球菌的抗感染药物的原型。

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