Temperate bacteriophages from chronic Pseudomonas aeruginosa lung infections show disease-specific changes in host range and modulate antimicrobial susceptibility

Tariq, Mohammad, Everest, Francesca, Cowley, Lauren A., Wright, Rosanna, Holt, Giles, Ingram, Hazel, Duignan, Liberty, Nelson, Andrew, Lanyon, Clare, Perry, Audrey, Perry, John D., Bourke, Stephen, Brockhurst, Michael A., Bridge, Simon, de Soyza, Anthony and Smith, Darren (2019) Temperate bacteriophages from chronic Pseudomonas aeruginosa lung infections show disease-specific changes in host range and modulate antimicrobial susceptibility. mSystems, 4 (4). e00191-18. ISSN 2379-5077

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Official URL: https://doi.org/10.1128/msystems.00191-18

Abstract

Temperate bacteriophages are a common feature of Pseudomonas aeruginosa genomes, but their role in chronic lung infections is poorly understood. This study was designed to identify the diverse communities of mobile P. aeruginosa phages by employing novel metagenomic methods, to determine cross infectivity, and to demonstrate the influence of phage infection on antimicrobial susceptibility. Mixed temperate phage populations were chemically mobilized from individual P. aeruginosa, isolated from patients with cystic fibrosis (CF) or bronchiectasis (BR). The infectivity phenotype of each temperate phage lysate was evaluated by performing a cross-infection screen against all bacterial isolates and tested for associations with clinical variables. We utilized metagenomic sequencing data generated for each phage lysate and developed a novel bioinformatic approach allowing resolution of individual temperate phage genomes. Finally, we used a subset of the temperate phages to infect P. aeruginosa PAO1 and tested the resulting lysogens for their susceptibility to antibiotics. Here, we resolved 105 temperate phage genomes from 94 lysates that phylogenetically clustered into 8 groups. We observed disease-specific phage infectivity profiles and found that phages induced from bacteria isolated from more advanced disease infected broader ranges of P. aeruginosa isolates. Importantly, when infecting PAO1 in vitro with 20 different phages, 8 influenced antimicrobial susceptibility. This study shows that P. aeruginosa isolated from CF and BR patients harbors diverse communities of inducible phages, with hierarchical infectivity profiles that relate to the progression of the disease. Temperate phage infection altered the antimicrobial susceptibility of PAO1 at subinhibitory concentrations of antibiotics, suggesting they may be precursory to antimicrobial resistance.

Item Type: Article
Uncontrolled Keywords: antimicrobial susceptibility, bacteriophages, bronchiectasis, cystic fibrosis, lysogenic, metagenomics, temperate
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 12 Jun 2019 10:26
Last Modified: 11 Oct 2019 09:17
URI: http://nrl.northumbria.ac.uk/id/eprint/39654

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