The phage lytic proteins from the Staphylococcus aureus bacteriophage vB_SauS-phiIPLA88 display multiple active catalytic domains and do not trigger staphylococcal resistance.

The phage lytic proteins from the Staphylococcus aureus bacteriophage vB_SauS-phiIPLA88 display multiple active catalytic domains and do not trigger staphylococcal resistance.
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来自金黄色葡萄球菌噬菌体 vB_SauS-phiIPLA88 的噬菌体裂解蛋白显示出多个活性催化结构域,并且不会引发葡萄球菌耐药性。

DOI:
10.1371/journal.pone.0064671
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
García P
García P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Rodríguez-Rubio L;Martínez B;Rodríguez A;Donovan DM;Götz F;García P

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世界范围内抗生素耐药性的增加使人们对使用噬菌体溶素来对抗病原菌重新产生了兴趣。在这项工作中,我们分析了三个噬菌体裂解蛋白产生的葡萄球菌肽聚糖的特异性切割位点。所研究的细胞壁裂解酶是来源于S.金黄色葡萄球菌噬菌体vB_SauS-phi-IPLA 88(phi-IPLA 88)和溶葡萄球菌酶与病毒体相关肽聚糖水解酶HydH 5之间的两种融合蛋白(HydH 5SH 3b和HydH 5Lyso)。我们确定这些蛋白质中存在的所有催化结构域都是活性的。此外,我们测试了对三种噬菌体裂解蛋白构建体中的任何一种的耐药性金黄色葡萄球菌的出现。耐甲氧西林金黄色葡萄在液体或平板培养物中细菌暴露于噬菌体裂解蛋白10个循环后,不能鉴定金黄色葡萄球菌。然而,观察到溶葡萄球菌酶抗性的快速增加(在液体培养中高达1000倍)。缺乏耐药性的发展支持使用噬菌体裂解蛋白作为未来治疗葡萄球菌感染的疗法。
The increase in antibiotic resistance world-wide revitalized the interest in the use of phage lysins to combat pathogenic bacteria. In this work, we analyzed the specific cleavage sites on the staphylococcal peptidoglycan produced by three phage lytic proteins. The investigated cell wall lytic enzymes were the endolysin LysH5 derived from the S. aureus bacteriophage vB_SauS-phi-IPLA88 (phi-IPLA88) and two fusion proteins between lysostaphin and the virion-associated peptidoglycan hydrolase HydH5 (HydH5SH3b and HydH5Lyso). We determined that all catalytic domains present in these proteins were active. Additionally, we tested for the emergence of resistant Staphylococcus aureus to any of the three phage lytic proteins constructs. Resistant S. aureus could not be identified after 10 cycles of bacterial exposure to phage lytic proteins either in liquid or plate cultures. However, a quick increase in lysostaphin resistance (up to 1000-fold in liquid culture) was observed. The lack of resistant development supports the use of phage lytic proteins as future therapeutics to treat staphylococcal infections.
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