Formation of therapeutic phage cocktail and endolysin to highly multi-drug resistant Acinetobacter baumannii: in vitro and in vivo study.
Formation of therapeutic phage cocktail and endolysin to highly multi-drug resistant Acinetobacter baumannii: in vitro and in vivo study.
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DOI：
10.22038/ijbms.2018.27307.6665
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发表时间：
2018-11
影响因子：
2.2
通讯作者：
Abdulamir AS
中科院分区：
文献类型：
--
作者：
Jasim HN;Hafidh RR;Abdulamir AS
噬菌体治疗是一种潜在的替代治疗鲍曼不动杆菌引起的感染，鲍曼不动杆菌是一种重要的医院病原体，在卫生条件差和冲突地区（如伊拉克），鲍曼不动杆菌对几乎所有常规抗菌药物都产生了耐药性。 噬菌体对高抗性的A.以形成治疗性噬菌体混合物，并提取和评价天然内溶素活性。在Al-Imamein Al-kadhimein Medical City Hospital采集细菌样本。噬菌体从巴格达市的不同地区分离，包括（土壤，污水，灌溉渠道）。噬菌体内溶素是从高度裂解的噬菌体中提取的，其在抑制区周围产生晕状外观。 多达23株广泛耐药和泛耐药（XDR，PDR）A. 136株鲍曼不动杆菌特异性溶菌。分离出鲍曼不动杆菌。每种细菌分离物对至少一种裂解性噬菌体敏感。因此，配制了噬菌体混合物，当与单独的裂解酶相比时，其显著地最小化了细菌对裂解酶裂解的抗性。而且，噬菌体鸡尾酒成功地治疗和挽救了所有A.鲍曼不动杆菌与未治疗组。此外，内溶素对A.在该研究中评估了鲍曼不动杆菌;内溶素显示在仅仅1小时的内溶素处理中细菌密度的有效抗菌活性（> 1 log）降低。 本研究中评估的噬菌体疗法显示出通过在体外和体内有效地裂解大多数XDR、PDR细菌来有效地解决“超级细菌”细菌问题的能力。并且，噬菌体混合物在治疗A方面被证明优于单噬菌体制剂的上级。鲍曼不动杆菌对抗菌药物的耐药率低得多。此外，天然内溶素的内在活性揭示了解决超级细菌病原体的有希望的结果。
Phage therapy is a potential alternative treatment for infections caused by Acinetobacter baumannii, a significant nosocomial pathogen, which has evolved resistance to almost all conventional antimicrobial drugs in poor hygiene and conflicts areas such as Iraq. Bacteriophages were isolated to highly resistant isolates of A. baumannii to form therapeutic phage cocktail, and to extract and evaluate native endolysin activity. Bacterial samples were collected in Al-Imamein Al-kadhimein Medical City Hospital. Phages were isolated from different regions in Baghdad city including (soil, sewage, irrigation channels). Phage endolysin was extracted from highly lytic phages that produced halo-like appearance around inhibition zone. Up to 23 isolates of extensive- and pan- drug resistant (XDR, PDR) A. baumannii were isolated from patients with various infections, and 136 lytic phages specific to A. baumannii were isolated. Each bacterial isolate was sensitive to at least one lytic phage. Accordingly, a phage cocktail was formulated which remarkably minimized bacterial resistance to lysis by phages when compared to individual lytic phages. And, the phage cocktail succeeded in treating and saving life of all bacteremic mice with A. baumannii versus the non-treated group. In addition, the endolysin native activity to A. baumannii was evaluated in this study; endolysin revealed a potent antibacterial activity (> 1 log) reduction of bacterial density in just one hour of endolysin treatment. The phage therapy assessed in this study showed an ability to efficiently solve the problems of “superbug” bacteria by lysing effectively most XDR, PDR bacteria in vitro and in vivo. And, phage cocktail was shown to be superior over single-phage preparations in treating A. baumannii with much less resistance rate to therapeutic phages. Furthermore, intrinsic activity of native endolysin revealed promising results to tackling superbug pathogens.