基于迭代进化的肠出血性大肠杆菌噬菌体鸡尾酒的抗菌效果评价  

Evaluation of the Antibacterial Efficacy of Enterohemorrhagic Escherichia coli Phage Cocktails Developed through Iterative Adaptive Evolution

作　　者：丁子韩 谢宇桢 曹晨昕 陈泉 刘慧 徐蓁禾 王壮 王启要[1,2,3] 刘琴 DING Zihan;XIE Yuzhen;CAO Chenxin;CHEN Quan;LIU Hui;XU Zhenhe;WANG Zhuang;WANG Qiyao;LIU Qin(State Key Laboratory of Bioreactor Engineering,East China University of Science and Technology,Shanghai 200237,China;Shanghai Engineering Research Center of Maricultured Animal Vaccines,Shanghai 201424,China;Aquatic Animal Diseases Research Laboratory,Ministry of Agriculture and Rural Affairs,Shanghai 201424,China)

机构地区：[1]华东理工大学生物反应器工程国家重点实验室,上海200237 [2]上海海洋动物疫苗工程技术研究中心,上海201424 [3]农业农村部水生动物疫病专业实验室,上海201424

出　　处：《华东理工大学学报（自然科学版）》2024年第6期832-839,共8页Journal of East China University of Science and Technology

基　　金：国家杰出青年科学基金(32025038);中央高校基本科研业务费专项资金(222201231540)。

摘　　要：分离到一株抗菌能力较差的新型噬菌体vB_EcoM_CRP22,通过模拟噬菌体与细菌在自然环境中的相互作用,开发了迭代适应性进化的方法使噬菌体感染噬菌体抗性突变菌株,显著提高了噬菌体对肠出血性大肠杆菌(EHEC)的抗菌效果,由噬菌体进化株组合成的鸡尾酒制剂感染细菌后36 h内能有效控制OD_(600)低于0.4。该实验为噬菌体疗法的发展提供了新思路。Enterohemorrhagic Escherichia coli(EHEC)is an important foodborne human pathogen that causes various severe intestinal diseases.Antibiotics are mainly used to control pathogenic bacteria.However,the extensive use of antibiotics increases antibiotics resistance and disrupts human flora,posing threats to public health security.Thus,it is necessary to develop alternative therapies to antibiotics.Phages are potential antibiotic alternatives with high host specificity,killing host bacteria without damaging other bacteria.However,the rapid emergence of phage-resistant bacteria remains a major challenge for phage therapy.Phage cocktails containing diverse phage strains have been identified as an effective strategy,although substantial isolation efforts are required which can be disadvantageous for treatments.In the ecosystem,phages adaptively evolve with bacteria.This process has been repeated in laboratory and diverse phage strains can be obtained.In this study,an Escherichia coli phage vB_EcoM_CRP22(CRP22)is isolated but demonstrates poorly antimicrobial against EHEC.An iterative adaptive evolution strategy is designed to obtain different phage strains targeting phage-resistant EHEC.Multiple evolved phages complement its host spectrum,leading to the enhanced antimicrobial efficiency of phage cocktails against EHEC.The phage cocktail consisting of 6 phage strains effectively control the OD_(600) value below 0.4 within 36 h post-infection.This work contributes to promoting the alternative of antibiotic therapies and provides a new insight into the development of phage therapy.

关 键 词：肠出血性大肠杆菌 噬菌体疗法 适应性进化 噬菌体鸡尾酒 抗菌效果 

分 类 号：Q939.9[生物学—微生物学]