Projects per year
Abstract
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
Original language | English |
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Article number | 106275 |
Number of pages | 10 |
Journal | Journal of Infection |
Volume | 89 |
Issue number | 5 |
Early online date | 23 Sept 2024 |
DOIs | |
Publication status | Published - Nov 2024 |
Keywords
- Bacterial
- Bacterial infections
- Bronchiectasis
- Drug resistance
- Genetic variation
- Lung
- Pseudomonas aeruginosa
- Whole genome sequencing
ASJC Scopus subject areas
- Microbiology (medical)
- Infectious Diseases
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Dive into the research topics of 'Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis'. Together they form a unique fingerprint.Projects
- 1 Active
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Understanding and Predicting the Evolution of Antibiotic Resistance in Human Infection (other institutions, joint lead Dundee/Sheffield Uni, Liverpool Uni))
Chalmers, J. (Investigator)
1/02/21 → 31/01/27
Project: Research