小柯机器人

美国匹兹堡大学Graham F. Hatfull、科罗拉多大学Jerry A. Nick等研究人员合作发现，宿主和病原体能够响应针对脓肿分枝杆菌肺部感染而设计的噬菌体。2022年5月13日，国际知名学术期刊《细胞》在线发表了这一成果

研究人员对一名患有难治性脓肿分枝杆菌肺部感染和严重囊性纤维化肺部疾病的男性患者静脉注射了两种噬菌体。这些噬菌体经过设计以增强其溶解脓肿杆菌的能力，并被特别挑选为对受试者的细菌分离物最有效的噬菌体。在同情性使用的情况下，研究人员使用分子和代谢测定结合临床评估来观察到了噬菌体诱导裂解的证据。噬菌体治疗前后的脓毒症分离物表现出遗传稳定性，多样性普遍下降，对噬菌体或抗生素的抗性没有增加。

对一种噬菌体的抗噬菌体中和抗体滴度随着时间的推移而增加，但在整个治疗过程中并不妨碍临床改善。受试者在第379天接受了肺移植，对切除的肺部进行系统的培养，没有发现脓肿杆菌。这项研究描述了晚期肺部疾病中成功的噬菌体治疗脓毒症的过程和相关标志物。

附：英文原文

Title: Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection

Author: Jerry A. Nick, Rebekah M. Dedrick, Alice L. Gray, Eszter K. Vladar, Bailey E. Smith, Krista G. Freeman, Kenneth C. Malcolm, L. Elaine Epperson, Nabeeh A. Hasan, Jo Hendrix, Kimberly Callahan, Kendra Walton, Brian Vestal, Emily Wheeler, Noel M. Rysavy, Katie Poch, Silvia Caceres, Valerie K. Lovell, Katherine B. Hisert, Vinicius Calado de Moura, Delphi Chatterjee, Prithwiraj De, Natalia Weakly, Stacey L. Martiniano, David A. Lynch, Charles L. Daley, Michael Strong, Fan Jia, Graham F. Hatfull, Rebecca M. Davidson

Issue&Volume: 2022-05-13

Abstract: Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject’s bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.

DOI: 10.1016/j.cell.2022.04.024

Source: https://www.cell.com/cell/fulltext/S0092-8674(22)00471-8