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首页> 外文期刊>Frontiers in Microbiology >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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The Bacteriophage EF-P29 Efficiently Protects against Lethal Vancomycin-Resistant Enterococcus faecalis and Alleviates Gut Microbiota Imbalance in a Murine Bacteremia Model

机译：噬菌体EF-P29可有效抵抗耐万古霉素的致死性粪肠球菌，并减轻小鼠细菌血症模型中肠道菌群的失衡。

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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 × 10~(5)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 × 10~(9)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.
机译：粪肠球菌正在世界范围内成为越来越重要的机会性病原体，尤其是因为它可以引起威胁生命的医院感染。由于多药耐药的粪肠球菌菌株的流行，治疗粪肠球菌的感染变得越来越困难。由于噬菌体对它们的细菌宿主显示出特异性，因此人们越来越关注使用噬菌体疗法来对抗多药耐药细菌感染的上升趋势。在这项研究中，我们分离了一种新的裂解性噬菌体EF-P29，它对粪肠球菌菌株（包括耐万古霉素的菌株）显示出高效率和广泛的宿主范围。 EF-P29基因组包含58,984 bp（39.97％G + C），包括101个开放阅读框，并且缺少已知的假定毒力因子，整合相关蛋白或抗生素抗性决定簇。在鼠类实验中，攻击后1小时单次腹膜内注射EF-P29（4×10〜（5）PFU）足以保护所有小鼠免受因耐万古霉素的粪肠球菌菌株感染而引起的菌血症。 （2×10〜（9）CFU /鼠标）。与未受保护的小鼠相比，在受EF-P29保护的小鼠的血液中，粪便肠球菌的计数被更快地消除了。我们还发现，外源性粪肠球菌的攻击导致小鼠肠道中肠球菌属（肠球菌科）成员的富集，这表明它可以进入肠道并在那里定居。噬菌体EF-P29减少了肠球菌属的菌落数量，并减轻了粪肠球菌攻击引起的肠道菌群失衡。这些数据表明，噬菌体EF-P29显示出作为全身性VREF感染的治疗方法的巨大潜力。因此，针对机会性病原体的噬菌体疗法也是可行的。应当控制噬菌体的剂量，并以适当的水平使用，以避免引起肠道菌群失衡。

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