Temperate bacteriophages from chronic Pseudomonas aeruginosa lung infections show disease-specific changes in host range and modulate antimicrobial susceptibility
| Autor: | Rosanna C. T. Wright, Andrew Nelson, Simon H. Bridge, Darren Smith, John D. Perry, Audrey Perry, Lauren A. Cowley, Anthony De Soyza, Clare Lanyon, Liberty A. M. Duignan, Giles Holt, Francesca Everest, Mohammad A. Tariq, Michael A. Brockhurst, Stephen Bourke, Hazel Ingram |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Temperate
bacteriophages Physiology medicine.drug_class bronchiectasis viruses Antibiotics lysogenic Biology medicine.disease_cause Antimicrobial susceptibility Biochemistry Microbiology Cystic fibrosis antimicrobial susceptibility Host-Microbe Biology cystic fibrosis 03 medical and health sciences Antibiotic resistance Lysogen Lysogenic cycle Genetics medicine Bacteriophages Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Infectivity 0303 health sciences metagenomics 030306 microbiology Pseudomonas aeruginosa biology.organism_classification C700 QR1-502 humanities Bronchiectasis Computer Science Applications Temperateness Modeling and Simulation Metagenomics Lysogenic Bacteria Research Article temperate |
| Zdroj: | mSystems, Vol 4, Iss 4 (2019) mSystems Tariq, M A, Everest, F L C, Cowley, L A, Wright, R, Holt, G S, Ingram, H, Duignan, L A M, Nelson, A, Lanyon, C V, Perry, A, Perry, J D, Bourke, S, Brockhurst, M A, Bridge, S H, De Soyza, A & Smith, D L 2019, ' Temperate Bacteriophages from Chronic Pseudomonas aeruginosa Lung Infections Show Disease-Specific Changes in Host Range and Modulate Antimicrobial Susceptibility ', mSystems, vol. 4, no. 4, e00191-18 . https://doi.org/10.1128/mSystems.00191-18 |
| ISSN: | 2379-5077 |
| DOI: | 10.1128/mSystems.00191-18 |
| Popis: | 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. 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. |
| Databáze: | OpenAIRE |
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