Global genomic diversity ofPseudomonas aeruginosain bronchiectasis

Abstract

AbstractBackgroundPseudomonas aeruginosais the dominant pathogen causing lung infections in people with both cystic fibrosis (CF) and bronchiectasis, associated with poorer outcomes. Unlike CF, bronchiectasis has been a neglected disease. More extensive genomic studies of larger bronchiectasis patient cohorts and within patient sampling are needed to improve understanding of the evolutionary mechanisms underpinningP. aeruginosainfections to guide novel and improved treatments.MethodsWe have performed genome sequencing of 2,854P. aeruginosaisolates from 180 patients attending clinics worldwide to analyse the genomic diversity between and within patient infections.ResultsWe observed high genetic diversity between infections with low incidence of highly transmissible strains. Our genomic data provide evidence for the mutational targets drivingP. aeruginosaevolution in bronchiectasis. Some functions found to gain mutations were comparable to CF, including biofilm and iron acquisition, whilst others highlighted distinct evolutionary paths in bronchiectasis such as pyocin production and resistance, and a novel efflux pump gene (PA1874). We also show a high incidence of antimicrobial resistance-associated mutations and acquired resistance genes, in particular multidrug efflux and fluoroquinolone resistance mechanisms.ConclusionsOur findings highlight important differences betweenP. aeruginosainfections in bronchiectasis and CF and provide evidence of the relatively minor role transmissible strains play in bronchiectasis. Our study provides a 10-fold increase in the available genomic data for these infections and is a global resource to improve our knowledge and understanding, to facilitate better patient outcomes.SummaryThe largest genomic study ofPseudomonas aeruginosabronchiectasis isolates to-date, providing an unprecedented global genomic resource. We highlight important differences between bronchiectasis and cystic fibrosis, including key genes under selection.