Pseudomonas aeruginosaadaptation and diversification in the non-cystic fibrosis bronchiectasis lung

Abstract

To characterise Pseudomonas aeruginosa populations during chronic lung infections of non-cystic fibrosis bronchiectasis patients, we used whole-genome sequencing to 1) assess the diversity of P. aeruginosa and the prevalence of multilineage infections; 2) seek evidence for cross-infection or common source acquisition; and 3) characterise P. aeruginosa adaptations.189 isolates, obtained from the sputa of 91 patients attending 16 adult bronchiectasis centres in the UK, were whole-genome sequenced.Bronchiectasis isolates were representative of the wider P. aeruginosa population. Of 24 patients from whom multiple isolates were examined, there were seven examples of multilineage infections, probably arising from multiple infection events. The number of nucleotide variants between genomes of isolates from different patients was in some cases similar to the variations observed between isolates from individual patients, implying the possible occurrence of cross-infection or common source acquisition.Our data indicate that during infections of bronchiectasis patients, P. aeruginosa populations adapt by accumulating loss-of-function mutations, leading to changes in phenotypes including different modes of iron acquisition and variations in biofilm-associated polysaccharides. The within-population diversification suggests that larger scale longitudinal surveillance studies will be required to capture cross-infection or common source acquisition events at an early stage.

Bronchiectasis Management

“…Predictors of therapy showed ICS use was, not surprisingly, associated with asthma, but the most striking finding is that patients with chronic Pseudomonas aeruginosa infection had higher rates of use of ICS, macrolides, and inhaled antibiotics, suggesting that US physicians recognize the poor prognosis associated with P aeruginosa and escalate pharmacotherapy accordingly. 8,9 The survey results support the data from the registry in showing that 55% of patients received ICS, whereas 40% received azithromycin, and 15% received inhaled tobramycin. The majority of online survey respondents (77%) had bronchiectasis associated with NTM.…”

Effects of low-molecular weight alcohols on bacterial viability

“…Moreover, the capsule provides protection against desiccation (18). Many highly adaptable Gram-negative rods such as P. aeruginosa can also produce biofilm-associated polysaccharides, becoming part of the most prevalent non-sporulated bacilli in hospital environment (19). As such, though EA inhibited P. aeruginosa growth in low concentrations, it could not efficiently kill it.…”

Metabolic and genetic basis for auxotrophies in Gram-negative species

“…Instead, we found that CEGs were highly conserved. Niche adaptation through small-scale loss-offunction mutations has been observed in strains including P. aeruginosa and Shigella (52)(53)(54). This result emphasizes that, in order to study auxotrophy development in host-adapted strains, future efforts should expand our workflow for the prediction of bacterial nutrient requirements (which is currently limited to the identification of genetic lesions at the gene level) to account for smaller-scale deleterious mutations.…”