The Bacteriophage EF-P29 Efficiently Protects against Lethal Vancomycin-Resistant Enterococcus faecalis and Alleviates Gut Microbiota Imbalance in a Murine Bacteremia Model.
The Bacteriophage EF-P29 Efficiently Protects against Lethal Vancomycin-Resistant Enterococcus faecalis and Alleviates Gut Microbiota Imbalance in a Murine Bacteremia Model.
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噬菌体 EF-P29 可有效防止致命的耐万古霉素粪肠球菌，并缓解鼠菌血症模型中的肠道微生物群失衡
DOI：
10.3389/fmicb.2017.00837
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发表时间：
2017
影响因子：
5.2
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Cheng M;Liang J;Zhang Y;Hu L;Gong P;Cai R;Zhang L;Zhang H;Ge J;Ji Y;Guo Z;Feng X;Sun C;Yang Y;Lei L;Han W;Gu J
粪肠球菌在世界范围内正成为一种日益重要的机会致病菌，特别是因为它可以引起危及生命的医院感染。治疗E.由于多重耐药大肠杆菌的流行，粪肠球菌感染变得越来越困难。粪菌菌株由于噬菌体对它们的细菌宿主显示出特异性，因此人们对使用噬菌体疗法来对抗多重耐药细菌感染的发病率上升越来越感兴趣。在本研究中，我们分离了一种新的裂解噬菌体EF-P29，它对大肠杆菌具有高效和广泛的宿主范围。粪菌菌株，包括万古霉素抗性菌株。EF-P29基因组包含58，984 bp（39.97% G+C），包括101个开放阅读框，并且缺乏已知的推定毒力因子、整合相关蛋白或抗生素抗性决定簇。在小鼠实验中，在攻击后1 h单次腹腔注射EF-P29（4 × 105 PFU）足以保护所有小鼠免受万古霉素耐药大肠杆菌感染引起的菌血症。粪肠球菌菌株（2 × 109 CFU/小鼠）。E.在EF-P29保护的小鼠的血液中，粪肠球菌菌落计数比未保护的小鼠更快地消除。我们还发现外源性E.粪菌攻击导致肠球菌属（肠球菌科）的成员在小鼠的肠道中富集，这表明它可以进入肠道并在那里定殖。噬菌体EF-P29可减少肠球菌属的菌落数，缓解由E.粪菌攻毒。这些数据表明，噬菌体EF-P29显示出作为系统性VREF感染的治疗性治疗的巨大潜力。因此，旨在治疗机会性病原体的噬菌体疗法也是可行的。噬菌体的剂量应控制在适当的水平，以避免引起肠道微生物群的不平衡。
Enterococcus faecalis is becoming an increasingly important opportunistic pathogen worldwide, especially because it can cause life-threatening nosocomial infections. Treating E. faecalis infections has become increasingly difficult because of the prevalence of multidrug-resistant E. faecalis strains. Because bacteriophages show specificity for their bacterial hosts, there has been a growth in interest in using phage therapies to combat the rising incidence of multidrug-resistant bacterial infections. In this study, we isolated a new lytic phage, EF-P29, which showed high efficiency and a broad host range against E. faecalis strains, including vancomycin-resistant strains. The EF-P29 genome contains 58,984 bp (39.97% G+C), including 101 open reading frames, and lacks known putative virulence factors, integration-related proteins or antibiotic resistance determinants. In murine experiments, the administration of a single intraperitoneal injection of EF-P29 (4 × 105 PFU) at 1 h after challenge was sufficient to protect all mice against bacteremia caused by infection with a vancomycin-resistant E. faecalis strain (2 × 109 CFU/mouse). E. faecalis colony counts were more quickly eliminated in the blood of EF-P29-protected mice than in unprotected mice. We also found that exogenous E. faecalis challenge resulted in enrichment of members of the genus Enterococcus (family Enterococcaceae) in the guts of the mice, suggesting that it can enter the gut and colonize there. The phage EF-P29 reduced the number of colonies of genus Enterococcus and alleviated the gut microbiota imbalance that was caused by E. faecalis challenge. These data indicate that the phage EF-P29 shows great potential as a therapeutic treatment for systemic VREF infection. Thus, phage therapies that are aimed at treating opportunistic pathogens are also feasible. The dose of phage should be controlled and used at the appropriate level to avoid causing imbalance in the gut microbiota.