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

Author

Listed:
  • Mei Liu

    (Texas A&M University
    Texas A&M University)

  • Adriana Hernandez-Morales

    (Texas A&M University
    Texas A&M University)

  • James Clark

    (Texas A&M University
    Texas A&M University)

  • Tram Le

    (Texas A&M University
    Texas A&M University)

  • Biswajit Biswas

    (Naval Medical Research Center)

  • Kimberly A. Bishop-Lilly

    (Naval Medical Research Center)

  • Matthew Henry

    (Naval Medical Research Center
    The Geneva Foundation)

  • Javier Quinones

    (Naval Medical Research Center
    The Geneva Foundation
    MilliporeSigma)

  • Logan J. Voegtly

    (Naval Medical Research Center
    Leidos)

  • Regina Z. Cer

    (Naval Medical Research Center)

  • Theron Hamilton

    (Naval Air Station)

  • Robert T. Schooley

    (University of California, San Diego)

  • Scott Salka

    (AmpliPhi Biosciences (now Armata Pharmaceuticals))

  • Ry Young

    (Texas A&M University
    Texas A&M University)

  • Jason J. Gill

    (Texas A&M University
    Texas A&M University)

Abstract

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.

Suggested Citation

  • Mei Liu & Adriana Hernandez-Morales & James Clark & Tram Le & Biswajit Biswas & Kimberly A. Bishop-Lilly & Matthew Henry & Javier Quinones & Logan J. Voegtly & Regina Z. Cer & Theron Hamilton & Robert, 2022. "Comparative genomics of Acinetobacter baumannii and therapeutic bacteriophages from a patient undergoing phage therapy," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31455-5
    DOI: 10.1038/s41467-022-31455-5
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