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Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child
EMBO Molecular Medicine ( IF 11.1 ) Pub Date : 2021-08-09 , DOI: 10.15252/emmm.202113936
Ameneh Khatami 1, 2 , Ruby C Y Lin 2, 3, 4 , Aleksandra Petrovic-Fabijan 3 , Sivan Alkalay-Oren 5, 6 , Sulaiman Almuzam 1 , Philip N Britton 1, 2 , Michael J Brownstein 7 , Quang Dao 8 , Joe Fackler 7 , Ronen Hazan 5 , Bri'Anna Horne 7 , Ran Nir-Paz 6 , Jonathan R Iredell 2, 3, 9
Affiliation  

Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7-year-old child. Monitoring of phage and bacterial kinetics allowed real-time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment. This was associated with transient fever and local pain and with evidence of marked upregulation of innate immunity genes in the host transcriptome. Adaptive immune responses appeared to develop after a week of therapy and some immunomodulatory elements were also observed to be upregulated.

中文翻译:

儿童辅助噬菌体治疗期间的细菌裂解、自噬和先天免疫反应

使用辅助噬菌体疗法是​​为了避免一名 7 岁儿童因广泛的慢性铜绿假单胞菌骨关节感染而造成灾难性后果。噬菌体和细菌动力学的监测允许实时噬菌体剂量调整,并且与人类宿主反应的标记一起,表明在开始辅助噬菌体治疗后两周内有显着的治疗效果。这些发现强烈表明,在治疗早期,细菌细胞或细胞碎片从深部骨感染部位释放到血流中。这与短暂发烧和局部疼痛有关,并且有证据表明宿主转录组中先天免疫基因的显着上调。治疗一周后似乎出现了适应性免疫反应,并且还观察到一些免疫调节元件上调。
更新日期:2021-09-07
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