中文摘要：多重耐药的细菌病原体数量正在急剧上升，预示着抗生素的黄金时代可能已经结束。噬菌体疗法很经典，通常使用溶菌噬菌体(杀死细胞的细菌特异性病毒)来对抗感染。最近使用噬菌体治疗病人获得成功，这激发了西医对噬菌体疗法更大的兴趣。也有人担心，广泛使用噬菌体疗法最终会导致耐噬菌体细菌在全球传播，导致该疗法失败。本文认为水平遗传转移（HGT）的各种机制在很大程度上促进了细菌种群和物种广泛获得抗生素耐药性，但对治疗性噬菌体不存在类似进化。噬菌体只感染特定基因型的细菌，限制其在治疗中的广泛应用，从而降低细菌通过HGT从远亲获得有益耐药基因的可能性。此外，考虑到聚集规律间隔短回文重复序列(CRISPR)免疫的HGT是否会阻碍噬菌体在治疗中的广泛使用，认为如果从一个类群中水平转移到其他类群，噬菌体特异性的CRISPR间隔区不太可能提供适应价值。可见，大规模的噬菌体治疗不太可能产生广泛的细菌耐药性进化选择。
外文摘要：Multi-drug resistant bacterial pathogens are alarmingly on the rise, signaling that the golden age of antibiotics may be over. Phage therapy is a classic approach that often employs strictly lytic bacteriophages (bacteria-specific viruses that kill cells) to combat infections. Recent success in using phages in patient treatment stimulates greater interest in phage therapy among Western physicians. But there is concern that widespread use of phage therapy would eventually lead to global spread of phage-resistant bacteria and widespread failure of the approach. Here, we argue that various mechanisms of horizontal genetic transfer (HGT) have largely contributed to broad acquisition of antibiotic resistance in bacterial populations and species, whereas similar evolution of broad resistance to therapeutic phages is unlikely. The tendency for phages to infect only particular bacterial genotypes limits their broad use in therapy, in turn reducing the likelihood that bacteria could acquire beneficial resistance genes from distant relatives via HGT. We additionally consider whether HGT of clustered regularly interspaced short palindromic repeats (CRISPR) immunity would thwart generalized use of phages in therapy, and argue that phage-specific CRISPR spacer regions from one taxon are unlikely to provide adaptive value if horizontallytransferred to other taxa. For these reasons, we conclude that broadscale phage therapy efforts are unlikely to produce widespread selection for evolution of bacterial resistance.
外文关键词：antibiotic resistance；bacteriophage；CRISPR；horizontal genetic transfer；fitness trade-off
作者：Cohan, FM；Zandi, M；Turner, PE
作者单位：Wesleyan Univ；Yale Univ；Yale Sch Med
期刊名称：VIRUS EVOLUTION
期刊影响因子：5.549
出版年份：2020
出版刊次：2
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