Center for Phage Technology, Texas A&M University, College Station, TX, USA.
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA.
Nat Commun. 2022 Jun 30;13(1):3776. doi: 10.1038/s41467-022-31455-5.
In 2016, a 68-year-old patient with a disseminated multidrug-resistant Acinetobacter baumannii infection was successfully treated using lytic bacteriophages. Here we report the genomes of the nine phages used for treatment and three strains of A. baumannii isolated prior to and during treatment. The phages used in the initial treatment are related, T4-like myophages. Analysis of 19 A. baumannii isolates collected before and during phage treatment shows that resistance to the T4-like phages appeared two days following the start of treatment. We generate complete genomic sequences for three A. baumannii strains (TP1, TP2 and TP3) collected before and during treatment, supporting a clonal relationship. Furthermore, we use strain TP1 to select for increased resistance to five of the phages in vitro, and identify mutations that are also found in phage-insensitive isolates TP2 and TP3 (which evolved in vivo during phage treatment). These results support that in vitro investigations can produce results that are relevant to the in vivo environment.
2016 年，一位 68 岁的患者因广泛耐药鲍曼不动杆菌感染而接受了溶菌噬菌体治疗，取得了成功。在此，我们报告了用于治疗的 9 种噬菌体和治疗前及治疗过程中分离出的 3 株鲍曼不动杆菌的基因组序列。用于初始治疗的噬菌体是相关的 T4 样噬菌体系列。对治疗前和治疗过程中收集的 19 株鲍曼不动杆菌分离株的分析表明，对 T4 样噬菌体的耐药性在治疗开始两天后出现。我们生成了治疗前和治疗过程中收集的 3 株鲍曼不动杆菌（TP1、TP2 和 TP3）的完整基因组序列，支持其具有克隆关系。此外，我们使用菌株 TP1 在体外选择对 5 种噬菌体的耐药性增加，并鉴定出在噬菌体不敏感的分离株 TP2 和 TP3 中也发现的突变（在噬菌体治疗过程中体内进化而来）。这些结果表明，体外研究可以产生与体内环境相关的结果。
