Harrington, NE, Kottara, A, Cagney, K, Shepherd, MJ, Grimsey, EM, Fu, T, Hull, RC, Chong, CE, Baker, KS, Childs, DZ et al (show 4 more authors)
(2024)
Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis.
Journal of Infection, 89 (5).
p. 106275.
ISSN 0163-4453, 1532-2742
Abstract
<h4>Objectives</h4>Pseudomonas aeruginosa is the most common pathogen in the bronchiectasis lung, associated with worsened outcomes. P. aeruginosa genomic studies in this context have been limited to single-country, European studies. We aimed to determine strain diversity, adaptation mechanisms, and AMR features to better inform treatment.<h4>Methods</h4>P. aeruginosa from 180 bronchiectasis patients in 15 countries, obtained prior to a phase 3, randomised clinical trial (ORBIT-3), were analysed by whole-genome sequencing. Phylogenetic groups and sequence types were determined, and between versus within patient genetic diversity compared using Analysis of Molecular Variance (AMOVA). The frequency of AMR-associated genes and mutations was also determined.<h4>Results</h4>A total of 2854 P. aeruginosa isolates were analysed, predominantly belonging to phylogenetic group 1 (83%, n = 2359). Genetic diversity was far greater between than within patients, responsible for >99.9% of total diversity (AMOVA: phylogroup 1: df = 145, P < 0.01). Numerous pathways were under selection, some shared with CF (e.g., motility, iron acquisition), some unique to bronchiectasis (e.g., novel efflux pump PA1874). Multidrug resistance features were also frequent.<h4>Conclusions</h4>We present a 10-fold increase in the availability of genomic data for P. aeruginosa in bronchiectasis, highlighting key distinctions with cystic fibrosis and potential targets for future treatments.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Pseudomonas aeruginosa, Pseudomonas Infections, Bronchiectasis, Anti-Bacterial Agents, Phylogeny, Drug Resistance, Multiple, Bacterial, Mutation, Genome, Bacterial, Female, Male, Genetic Variation, Whole Genome Sequencing |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 19 Sep 2024 08:50 |
| Last Modified: | 25 Oct 2024 17:37 |
| DOI: | 10.1016/j.jinf.2024.106275 |
| Open Access URL: | https://www.sciencedirect.com/science/article/pii/... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3184593 |
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