中文摘要：脓肿分枝杆菌是一种机会致病菌，其治疗受广泛的多药耐药影响。尽管脓肿分枝杆菌分离株的噬菌体敏感谱尚不清楚，但用噬菌体治疗脓肿分枝杆菌感染不失为一种潜在的替代方法。本文对近期临床分离的82株脓肿杆菌的噬菌体感染谱进行了测定，发现菌落形态粗糙或光滑是噬菌体易感性的关键指标。任何噬菌体都不能有效杀死光滑菌株，而80%的粗糙菌株受到感染并被至少一种噬菌体有效杀死。用于治疗粗糙型菌感染的噬菌体包括宿主范围相对较广的噬菌体、耻垢分枝杆菌噬菌体的宿主范围突变体，以及从整合原噬菌体衍生的溶性传播病毒。粗糙的菌落形态是由于糖肽类合成基因mps1和mps2发生了缺失突变，不能像噬菌体抗性的常见途径那样逆转成为平滑型。尽管聚酮合成、uvrD2及rpoZ的突变可能会引起抗性，但它们也可能会影响体在内存活，因此耐药性并不常见。扩展后的治疗用噬菌体库和耐药谱显示，几种或单一噬菌体适用于控制粗糙菌株的感染。
重点：由于抗生素耐药性广泛存在，治疗脓肿分枝杆菌感染的囊肿性纤维化患者难度很大。裂解噬菌体的治疗应用提出了一种新的潜在策略，但临床脓肿分枝杆菌分离株之间差异巨大，因此在治疗前需确定噬菌体的敏感性。对噬菌体感染的变异及其决定因素的阐明，治疗用候选噬菌体库的扩展，以及对噬菌体耐药机制更深入的了解，大大提高了广泛实施治疗脓肿分枝杆菌感染的新方案的潜力。
外文摘要：Mycobacterium abscessus is an opportunistic pathogen whose treatment is confounded by widespread multidrug resistance. The therapeutic use of bacteriophages against Mycobacterium abscessus infections offers a potential alternative approach, although the spectrum of phage susceptibilities among M. abscessus isolates is not known. We determined the phage infection profiles of 82 M. abscessus recent clinical isolates and find that colony morphotype & mdash;rough or smooth & mdash;is a key indicator of phage susceptibility. None of the smooth strains are efficiently killed by any phages, whereas 80% of rough strains are infected and efficiently killed by at least one phage. The repertoire of phages available for potential therapy of rough morphotype infections includes those with relatively broad host ranges, host range mutants of Mycobacterium smegmatis phages, and lytically propagated viruses derived from integrated prophages. The rough colony morphotype results from indels in the glycopeptidolipid synthesis genes mps1 and mps2, negating reversion to smooth as a common route to phage resistance. Resistance is thus rare, and although mutations in polyketide synthesis, uvrD2, and rpoZ can confer resistance, these likely also impair survival in vivo. The expanded therapeutic repertoire and the resistance profiles show that small cocktails or single phages could be suitable for controlling infections with rough strains.
IMPORTANCE Mycobacterium abscessus infections in cystic fibrosis patients are challenging to treat due to widespread antibiotic resistance. The therapeutic use of lytic bacteriophages presents a new potential strategy, but the great variation among clinical M. abscessus isolates demands determination of phage susceptibility prior to therapy. Elucidation of the variation in phage infection and factors determining it, expansion of the suite of therapeutic phage candidates, and a greater understanding of phage resistance mechanisms substantially advances the potential for broad implementation of new therapeutic options for M. abscessus infections.
外文关键词：Mycobacterium abscessus；bacteriophage therapy；bacteriophages
作者：Dedrick, RM；Smith, BE；Garlena, RA；Russell, DA；Aull, HG；Mahalingam, V；Divens, AM；Guerrero-Bustamante, CA；Zack, KM；Abad, L；Gauthier, CH；Jacobs-Sera, D；Hatfull, GF
作者单位：Univ Pittsburgh；West Virginia Univ
期刊名称：MBIO
期刊影响因子：4.778
出版年份：2021
出版刊次：2
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