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Fighting Fire with Fire: Phage Potential for the Treatment of E. coli O157 Infection

机译:用火扑救:治疗大肠杆菌O157感染的噬菌体潜力

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摘要

Hemolytic–uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like Escherichia coli (STEC), including E. coli O157:H7. Shiga toxin is encoded by resident prophages present within this bacterium, and both its production and release depend on the induction of Shiga toxin-encoding prophages. Consequently, treatment of STEC infections tend to be largely supportive rather than antibacterial, in part due to concerns about exacerbating such prophage induction. Here we explore STEC O157:H7 prophage induction in vitro as it pertains to phage therapy—the application of bacteriophages as antibacterial agents to treat bacterial infections—to curtail prophage induction events, while also reducing STEC O157:H7 presence. We observed that cultures treated with strictly lytic phages, despite being lysed, produce substantially fewer Shiga toxin-encoding temperate-phage virions than untreated STEC controls. We therefore suggest that phage therapy could have utility as a prophylactic treatment of individuals suspected of having been recently exposed to STEC, especially if prophage induction and by extension Shiga toxin production is not exacerbated.
机译:溶血尿毒综合症是一种威胁生命的疾病,最常与产生志贺毒素的微生物(如大肠杆菌(STEC),包括大肠杆菌O157:H7)相关。志贺毒素由该细菌中存在的常驻噬菌体编码,并且其产生和释放均依赖于编码志贺毒素的噬菌体的诱导。因此,对STEC感染的治疗往往在很大程度上是支持性的,而不是抗菌的,部分原因是由于担心加剧这种前兆诱导作用。在这里,我们探讨了STEC O157:H7噬菌体的体外诱导,因为它与噬菌体疗法有关(噬菌体作为抗菌剂用于治疗细菌感染),以减少噬菌体的诱导事件,同时也减少了STEC O157:H7的存在。我们观察到,用严格裂解的噬菌体处理的培养物尽管被裂解,但与未处理的STEC对照相比,产生的志贺毒素编码温带噬菌体病毒体明显减少。因此,我们建议噬菌体疗法可以作为怀疑最近暴露于STEC的个体的预防方法,尤其是如果不加剧前噬菌体诱导和志贺毒素产生的情况。

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