Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis
Therapeutic Effects of Intravitreously Administered Bacteriophage in a Mouse Model of Endophthalmitis Caused by Vancomycin-Sensitive or -Resistant Enterococcus faecalis
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DOI：
10.1128/aac.01088-19
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发表时间：
2019-11-01
影响因子：
4.9
通讯作者：
Fukushima, Atsuki
中科院分区：
文献类型：
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作者：
Kishimoto, Tatsuma;Ishida, Waka;Fukushima, Atsuki
肠球菌感染引起的眼内炎进展迅速，常常导致严重和不可逆转的视力丧失。鉴于万古霉素耐药粪肠球菌引起的这种情况的频率越来越高，迫切需要开发新的治疗方法。我们已经证明了噬菌体Phi EF24C-P2在由万古霉素敏感（EF24）或万古霉素耐药（VRE2）大肠杆菌引起的眼内炎小鼠模型中的治疗潜力。在EF24、VRE2和来自粪肠杆菌相关术后眼内炎患者的临床分离物的浊度降低试验中，噬菌体Phi EF24C-P2诱导了快速而明显的细菌裂解。将EF24或VRE2 （1 × 10(4)个细胞）注入玻璃体诱导小鼠眼内炎。感染后24 h，眼内活菌数增加至100 × 10(7) CFU，髓过氧化物酶活性增加，可见眼内中性粒细胞浸润。在注射EF24或VRE2后6小时，通过玻璃体内注射Phi EF24C-P2，以眼底可视性丧失为基础的临床评分以及眼内活菌数量和髓过氧化物酶活性水平均显著降低。然而，组织病理学分析显示，在噬菌体处理的眼睛中，炎症细胞大量浸润和视网膜脱离，这些细胞的数量大大减少，并且在噬菌体处理的眼睛中保持了视网膜结构的完整性。因此，我们的研究结果表明，玻璃体内噬菌体治疗是治疗由万古霉素敏感或耐药的粪肠杆菌引起的眼内炎的潜在治疗方法。
Endophthalmitis due to infection with Enterococcus spp. progresses rapidly and often results in substantial and irreversible vision loss. Given that the frequency of this condition caused by vancomycin-resistant Enterococcus faecalis has been increasing, the development of novel therapeutics is urgently required. We have demonstrated the therapeutic potential of bacteriophage Phi EF24C-P2 in a mouse model of endophthalmitis caused by vancomycin-sensitive (EF24) or vancomycin-resistant (VRE2) strains of E. faecalis. Phage Phi EF24C-P2 induced rapid and pronounced bacterial lysis in turbidity reduction assays with EF24, VRE2, and clinical isolates derived from patients with E. faecalis-related postoperative endophthalmitis. Endophthalmitis was induced in mice by injection of EF24 or VRE2 (1 X 10(4) cells) into the vitreous. The number of viable bacteria in the eye increased to > 1 X 10(7) CFU, and neutrophil infiltration into the eye was detected as an increase in myeloperoxidase activity at 24 h after infection. A clinical score based on loss of visibility of the fundus as well as the number of viable bacteria and the level of myeloperoxidase activity in the eye were all significantly decreased by intravitreous injection of Phi EF24C-P2 6 h after injection of EF24 or VRE2. Whereas histopathologic analysis revealed massive infiltration of inflammatory cells and retinal detachment in vehicle-treated eyes, the number of these cells was greatly reduced and retinal structural integrity was preserved in phage-treated eyes. Our results thus suggest that intravitreous phage therapy is a potential treatment for endophthalmitis caused by vancomycin-sensitive or -resistant strains of E. faecalis.