中文摘要：目前，噬菌体疗法是传统抗生素治疗的重要补充。然而，噬菌体耐药性的出现成为了这一抗菌策略可持续实施的主要障碍。通过综合基因组学和微生物学研究，揭示了受体修饰对靶向荚膜噬菌体，包括荚膜生物合成簇中的逃逸突变或胞外多糖的质变-将克隆转化为黏液变体的抗性。这些变异株对同一受体特异性的噬菌体产生交叉抗性，但对利用其他受体的噬菌体敏感。肺炎克雷伯菌主要毒力因子荚膜的缺失/修饰，对种群健康没有显著影响，也不能保护细菌不受先天免疫反应的影响。不过，在含有bla(CTX-M)、ant(3”)、sul2、folA、mph(E)/mph(G)基因的肺炎克雷伯菌77质粒中，使用噬菌体能促使细菌去除多药耐药簇。新出现的细菌对病毒感染的耐药性将进化导向所需的群体属性，并突出了联合抗生素-噬菌体协同治疗肺炎克雷伯菌的潜力。
外文摘要：Bacteriophage therapy is currently being evaluated as a critical complement to traditional antibiotic treatment. However, the emergence of phage resistance is perceived as a major hurdle to the sustainable implementation of this antimicrobial strategy. By combining comprehensive genomics and microbiological assessment, we show that the receptor-modification resistance to capsule-targeting phages involves either escape mutation(s) in the capsule biosynthesis cluster or qualitative changes in exopolysaccharides, converting clones to mucoid variants. These variants introduce cross-resistance to phages specific to the same receptor yet sensitize to phages utilizing alternative ones. The loss/modification of capsule, the main Klebsiella pneumoniae virulence factor, did not dramatically impact population fitness, nor the ability to protect bacteria against the innate immune response. Nevertheless, the introduction of phage drives bacteria to expel multidrug resistance clusters, as observed by the large deletion in K. pneumoniae 77 plasmid containing bla(CTX-M), ant(3 ''), sul2, folA, mph(E)/mph(G) genes. The emerging bacterial resistance to viral infection steers evolution towards desired population attributes and highlights the synergistic potential for combined antibiotic-phage therapy against K. pneumoniae.
作者：Majkowska-Skrobek, G；Markwitz, P；Sosnowska, E；Lood, C；Lavigne, R；Drulis-Kawa, Z
作者单位：Univ Wroclaw；Katholieke Univ Leuven
期刊名称：ENVIRONMENTAL MICROBIOLOGY
期刊影响因子：4.933
出版年份：2021
出版刊次：
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