Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis

J Infect. 2024 Nov;89(5):106275. doi: 10.1016/j.jinf.2024.106275. Epub 2024 Sep 16.

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.

Keywords: Bacterial; Bacterial infections; Bronchiectasis; Drug resistance; Genetic variation; Lung; Pseudomonas aeruginosa; Whole genome sequencing.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bronchiectasis* / genetics
  • Bronchiectasis* / microbiology
  • Drug Resistance, Multiple, Bacterial / genetics
  • Female
  • Genetic Variation*
  • Genome, Bacterial
  • Humans
  • Male
  • Mutation
  • Phylogeny*
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa* / genetics
  • Pseudomonas aeruginosa* / isolation & purification
  • Whole Genome Sequencing*

Substances

  • Anti-Bacterial Agents