Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility

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 cr...

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Autores principales:	Mohammad A. Tariq, Francesca L. C. Everest, Lauren A. Cowley, Rosanna Wright, Giles S. Holt, Hazel Ingram, Liberty A. M. Duignan, Andrew Nelson, Clare V. Lanyon, Audrey Perry, John D. Perry, Stephen Bourke, Michael A. Brockhurst, Simon H. Bridge, Anthony De Soyza, Darren L. Smith
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	antimicrobial susceptibility bacteriophages bronchiectasis cystic fibrosis lysogenic metagenomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/541144b34cce4ebea790c30a2eeabd38
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spelling	oai:doaj.org-article:541144b34cce4ebea790c30a2eeabd382021-12-02T18:25:16ZTemperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility10.1128/mSystems.00191-182379-5077https://doaj.org/article/541144b34cce4ebea790c30a2eeabd382019-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00191-18https://doaj.org/toc/2379-5077ABSTRACT 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. IMPORTANCE Pseudomonas aeruginosa is a key opportunistic respiratory pathogen in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. The genomes of these pathogens are enriched with mobile genetic elements including diverse temperate phages. While the temperate phages of the Liverpool epidemic strain have been shown to be active in the human lung and enhance fitness in a rat lung infection model, little is known about their mobilization more broadly across P. aeruginosa in chronic respiratory infection. Using a novel metagenomic approach, we identified eight groups of temperate phages that were mobilized from 94 clinical P. aeruginosa isolates. Temperate phages from P. aeruginosa isolated from more advanced disease showed high infectivity rates across a wide range of P. aeruginosa genotypes. Furthermore, we showed that multiple phages altered the susceptibility of PAO1 to antibiotics at subinhibitory concentrations.Mohammad A. TariqFrancesca L. C. EverestLauren A. CowleyRosanna WrightGiles S. HoltHazel IngramLiberty A. M. DuignanAndrew NelsonClare V. LanyonAudrey PerryJohn D. PerryStephen BourkeMichael A. BrockhurstSimon H. BridgeAnthony De SoyzaDarren L. SmithAmerican Society for Microbiologyarticleantimicrobial susceptibilitybacteriophagesbronchiectasiscystic fibrosislysogenicmetagenomicsMicrobiologyQR1-502ENmSystems, Vol 4, Iss 4 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial susceptibility bacteriophages bronchiectasis cystic fibrosis lysogenic metagenomics Microbiology QR1-502
spellingShingle	antimicrobial susceptibility bacteriophages bronchiectasis cystic fibrosis lysogenic metagenomics Microbiology QR1-502 Mohammad A. Tariq Francesca L. C. Everest Lauren A. Cowley Rosanna Wright Giles S. Holt Hazel Ingram Liberty A. M. Duignan Andrew Nelson Clare V. Lanyon Audrey Perry John D. Perry Stephen Bourke Michael A. Brockhurst Simon H. Bridge Anthony De Soyza Darren L. Smith Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility
description	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. IMPORTANCE Pseudomonas aeruginosa is a key opportunistic respiratory pathogen in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis. The genomes of these pathogens are enriched with mobile genetic elements including diverse temperate phages. While the temperate phages of the Liverpool epidemic strain have been shown to be active in the human lung and enhance fitness in a rat lung infection model, little is known about their mobilization more broadly across P. aeruginosa in chronic respiratory infection. Using a novel metagenomic approach, we identified eight groups of temperate phages that were mobilized from 94 clinical P. aeruginosa isolates. Temperate phages from P. aeruginosa isolated from more advanced disease showed high infectivity rates across a wide range of P. aeruginosa genotypes. Furthermore, we showed that multiple phages altered the susceptibility of PAO1 to antibiotics at subinhibitory concentrations.
format	article
author	Mohammad A. Tariq Francesca L. C. Everest Lauren A. Cowley Rosanna Wright Giles S. Holt Hazel Ingram Liberty A. M. Duignan Andrew Nelson Clare V. Lanyon Audrey Perry John D. Perry Stephen Bourke Michael A. Brockhurst Simon H. Bridge Anthony De Soyza Darren L. Smith
author_facet	Mohammad A. Tariq Francesca L. C. Everest Lauren A. Cowley Rosanna Wright Giles S. Holt Hazel Ingram Liberty A. M. Duignan Andrew Nelson Clare V. Lanyon Audrey Perry John D. Perry Stephen Bourke Michael A. Brockhurst Simon H. Bridge Anthony De Soyza Darren L. Smith
author_sort	Mohammad A. Tariq
title	Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility
title_short	Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility
title_full	Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility
title_fullStr	Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility
title_full_unstemmed	Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility
title_sort	temperate bacteriophages from chronic <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> lung infections show disease-specific changes in host range and modulate antimicrobial susceptibility
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/541144b34cce4ebea790c30a2eeabd38
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Temperate Bacteriophages from Chronic <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility

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