Journal Article

Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy

Biswas, Biswajit, Hernandez-Morales, Adriana, Voegtly, Logan J., Salka, Scott, Gill, Jason J., Henry, Matthew, Bishop-Lilly, Kimberly A., Quinones, Javier, Young, Ry, Cer, Regina Z., Clark, James, Liu, Mei, Hamilton, Theron, Schooley, Robert T., Le, Tram

2022

Overview

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. A patient with a multidrug-resistant bacterial infection was successfully treated in 2016 using phage therapy. Here, the authors sequence the genomes of the therapeutic phages and three bacterial strains isolated before and during treatment, and show that the same mutations conferring phage resistance are found in in vitro-generated mutants and in phage-insensitive strains isolated from the patient.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 45/22 / 45/23 / 631/326/107 / 631/326/1321 / 631/326/22/1434 / 692/699/255/1318 / Acinetobacter baumannii / Acinetobacter baumannii - genetics / Acinetobacter Infections - therapy / Aged / Bacterial diseases / Bacterial infections / Bacteriophages - genetics / Genomes / Genomics / Humanities and Social Sciences / Humans / In vivo methods and tests / multidisciplinary / Multidrug resistance / Mutation / Patients / Phage Therapy / Phages / Science / Science (multidisciplinary) / Strains (organisms)