阴沟肠杆菌
噬菌体疗法
溶解循环
噬菌体
微生物学
菌血症
生物
肠杆菌
碳青霉烯
鲍曼不动杆菌
肠杆菌科
抗生素
病毒学
铜绿假单胞菌
细菌
病毒
大肠杆菌
基因
遗传学
生物化学
作者
Shi-Yong Fu,Xiuzhen Chen,Peng-Cheng Yi,Jie Gao,Weixiao Wang,Siyu Gu,Jinghan Gao,Du-Xian Liu,Hanfeng Xu,Yi Zeng,Chunmei Hu,Qin Zheng,Wei Chen
摘要
ABSTRACT The increase in multidrug-resistant (MDR) Enterobacter cloacae complex (ECC) infections, particularly those resistant to carbapenems, underscores the urgent need for alternative therapies. Phage therapy, with its specific bactericidal action, offers a promising solution. However, there remains a shortage of well-characterized ECC-targeting phages, and dosing and timing optimization for ECC-specific phage cocktails is largely unexplored. In this study, we isolated and characterized three novel lytic phages with diverse genome sizes and host ranges. Notably, ФEBU8 demonstrated broad-spectrum activity, lysing both Enterobacter species and Acinetobacter baumannii . ФECL22 displayed stability across a wide temperature range (4–50°C), pH tolerance (6–10), and a burst size of 19 PFU/cell, with OmpA identified as its receptor. Our formulated phage cocktail, comprising ФEBU8, ФECL22, and ФECL30, effectively rescued mice with E. cloacae bacteremia in a dose-dependent manner, with a mid-dose regimen showing particularly strong efficacy. Immediate phage administration achieved full survival, whereas a combined prophylactic and therapeutic regimen (“−24 + 6”) also resulted in 100% survival. These findings highlight the critical roles of dosing and timing in optimizing phage therapy for carbapenem-resistant Enterobacter infections, with prophylactic use providing a valuable window for delayed treatment and a promising strategy for combating severe bacterial infections.
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