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以毒攻毒:噬菌体治疗O157感染的潜力

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

作者信息

Howard-Varona Cristina, Vik Dean R, Solonenko Natalie E, Li Yueh-Fen, Gazitua M Consuelo, Chittick Lauren, Samiec Jennifer K, Jensen Aubrey E, Anderson Paige, Howard-Varona Adrian, Kinkhabwala Anika A, Abedon Stephen T, Sullivan Matthew B

机构信息

Department of Microbiology, The Ohio State University, Columbus, OH 43210, USA.

EpiBiome, Inc., 29528 Union City blvd, Union City, CA 94587, USA.

出版信息

Antibiotics (Basel). 2018 Nov 16;7(4):101. doi: 10.3390/antibiotics7040101.

Abstract

Hemolytic⁻uremic syndrome is a life-threating disease most often associated with Shiga toxin-producing microorganisms like (STEC), including 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.

摘要

溶血尿毒综合征是一种危及生命的疾病,最常与产志贺毒素的微生物如肠出血性大肠杆菌(STEC)相关,包括O157:H7。志贺毒素由该细菌内的原噬菌体编码,其产生和释放均依赖于志贺毒素编码原噬菌体的诱导。因此,STEC感染的治疗往往主要是支持性的而非抗菌性的,部分原因是担心会加剧这种原噬菌体的诱导。在此,我们探讨了体外STEC O157:H7原噬菌体的诱导情况,因为这与噬菌体疗法(将噬菌体作为抗菌剂用于治疗细菌感染)相关,目的是减少原噬菌体诱导事件,同时也减少STEC O157:H7的存在。我们观察到,用严格裂解性噬菌体处理的培养物,尽管被裂解,但产生的编码志贺毒素的温和噬菌体病毒粒子比未处理的STEC对照物少得多。因此,我们认为噬菌体疗法可作为对疑似近期接触过STEC的个体的预防性治疗手段,特别是在原噬菌体诱导以及由此产生的志贺毒素生成未加剧的情况下。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b780/6315980/66ed2dccb41c/antibiotics-07-00101-g001.jpg

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