Endolysin LysEF-P10 shows potential as an alternative treatment strategy for multidrug-resistant Enterococcus faecalis infections.
Endolysin LysEF-P10 shows potential as an alternative treatment strategy for multidrug-resistant Enterococcus faecalis infections.
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内溶素 LysEF-P10 显示出作为多重耐药粪肠球菌感染的替代治疗策略的潜力
DOI：
10.1038/s41598-017-10755-7
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发表时间：
2017-08-31
影响因子：
4.6
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Cheng M;Zhang Y;Li X;Liang J;Hu L;Gong P;Zhang L;Cai R;Zhang H;Ge J;Ji Y;Guo Z;Feng X;Sun C;Yang Y;Lei L;Han W;Gu J
噬菌体溶素可以水解细菌细胞壁，在对抗革兰氏阳性病原体方面显示出巨大的潜力。在这项研究中，LysEF-P10，一个新的溶素来自一个分离的粪肠球菌噬菌体EF-P10，作为一种替代治疗多重耐药大肠杆菌的潜力。粪便感染，进行了研究。LysEF-P10与其最接近的同源物只有61%的氨基酸同一性。表达了四种蛋白质：LysEF-P10、半胱氨酸、组氨酸依赖性酰胺水解酶/肽酶（AMH）结构域（LysEF-P10 C）、推定结合结构域（LysEF-P10 B）和融合重组蛋白（LysEF-P10 B-绿色荧光蛋白）。只有LysEF-P10对大肠杆菌表现出高效、广谱的杀菌活性。粪便。通过三维结构预测、BLAST和突变分析，确定了Cys-His-Asn三联体和钙结合位点等关键功能残基。我们还发现，钙可以转换LysEF-P10之间的活动和非活动状态，LysEF-P10 B是负责结合E。粪细胞单次给予LysEF-P10（5 μg）足以保护小鼠免受致死性万古霉素耐药粪肠球菌（VREF）感染，LysEF-P10特异性抗体不影响其杀菌活性或治疗效果。此外，LysEF-P10减少了肠球菌的菌落数量，缓解了VREF引起的肠道微生物群失衡。这些结果表明LysEF-P10可能是多药耐药大肠杆菌的替代治疗。粪便感染
Phage-derived lysins can hydrolyse bacterial cell walls and show great potential for combating Gram-positive pathogens. In this study, the potential of LysEF-P10, a new lysin derived from a isolated Enterococcus faecalis phage EF-P10, as an alternative treatment for multidrug-resistant E. faecalis infections, was studied. LysEF-P10 shares only 61% amino acid identity with its closest homologues. Four proteins were expressed: LysEF-P10, the cysteine, histidine-dependent amidohydrolase/peptidase (CHAP) domain (LysEF-P10C), the putative binding domain (LysEF-P10B), and a fusion recombination protein (LysEF-P10B-green fluorescent protein). Only LysEF-P10 showed highly efficient, broad-spectrum bactericidal activity against E. faecalis. Several key functional residues, including the Cys-His-Asn triplet and the calcium-binding site, were confirmed using 3D structure prediction, BLAST and mutation analys. We also found that calcium can switch LysEF-P10 between its active and inactive states and that LysEF-P10B is responsible for binding E. faecalis cells. A single administration of LysEF-P10 (5 μg) was sufficient to protect mice against lethal vancomycin-resistant Enterococcus faecalis (VREF) infection, and LysEF-P10-specific antibody did not affect its bactericidal activity or treatment effect. Moreover, LysEF-P10 reduced the number of Enterococcus colonies and alleviated the gut microbiota imbalance caused by VREF. These results indicate that LysEF-P10 might be an alternative treatment for multidrug-resistant E. faecalis infections.
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影响因子：
4.1
作者：
Fischetti, Vincent A.
通讯作者：
Fischetti, Vincent A.
影响因子：
6
作者：
Galli, Stephen J.
通讯作者：
Galli, Stephen J.
影响因子：
14.9
作者：
Grant JR;Stothard P
通讯作者：
Stothard P
影响因子：
11.8
作者：
Courvalin, P
通讯作者：
Courvalin, P
DOI：
10.1073/pnas.85.3.914
发表时间：
1988-02-01
影响因子：
11.1
作者：
GARCIA, E;GARCIA, JL;LOPEZ, R
通讯作者：
LOPEZ, R