The deletion of TonB-dependent receptor genes is part of the genome reduction process that occurs during adaptation ofPseudomonas aeruginosato the cystic fibrosis lung

Abstract

Chronic Pseudomonas aeruginosa infections are the main cause of morbidity among patients with cystic fibrosis (CF) due to persistent lung inflammation caused by interaction between this bacterium and the immune system. Longitudinal studies of clonally related isolates of a dominant CF clone have indicated that genome reduction frequently occurs during adaptation of P. aeruginosa in the CF lung. In this study, we have evaluated the P. aeruginosa population structure of patients attending the Universitair Ziekenhuis Brussel (UZ Brussel) CF reference center using a combination of genotyping methods. Although the UZ Brussel P. aeruginosa CF population is characterized by the absence of a dominant CF clone, some potential interpatient transmissions could be detected. Interestingly, one of these clones showed deletion of the alternative type I ferripyoverdine receptor gene fpvB. Furthermore, we found that several other TonB-dependent receptors are deleted as well. The genome of one potentially transmissible CF clone was sequenced, revealing large deleted regions including all type III secretion system genes and several virulence genes. Remarkably, a large number of deleted genes are shared between the P. aeruginosa CF clone described in this study and isolates belonging to the dominant Copenhagen CF DK2 clone, suggesting parallel evolution.

Habitat‐associated skew of clone abundance in the Pseudomonas aeruginosa population

“…FpvA ‐negative P. aeruginosa strains were 1.9‐fold more frequent among disease than among environmental isolates ( P = 0.0084, Fisher's exact test). FpvB ‐non‐typable strains had a share of 12.8% among the CF isolates and of 7.9% among all other strains ( P = 0.00065) confirming a previous report that the fpvB gene locus is prone to deletion in CF lungs (Dingemans et al ., ). Consistent with the lower proportion of FpvB to recognize type I pyoverdine, the type I fpvA receptor gene was significantly underrepresented among isolates from the CF airways (34.1%) compared with those from all other habitats (41.5%, P = 0.00076).…”

Pseudomonas aeruginosa renews its virulence factors

“…In addition, the PA7 genome possesses 18 genomic islands inserted in regions of genomic plasticity (RGP) that are absent in PAO1 and PA14. Since this first publication in 2010 and the advances in nextgeneration sequencing technology, the genomes of 14 'PA7-like strains' (Dingemans et al, 2014;Boukerb et al, 2015;Kos et al, 2015;Mai-Prochnow et al, 2015;van Belkum et al, 2015) and of five related strains (Dingemans et al, 2014;Boukerb et al, 2015;van Belkum et al, 2015) have been fully sequenced, deposited in NCBI and made available at Pseudomonas genome project website (www.pseudomonas.com) ( Table 1).…”

“…Another example is a specific bacteriocin, pyocin S6, released by the exlA1 strain CF_PA39 (Dingemans et al, 2014). Bacteriocins, called pyocins when secreted by P. aeruginosa, are produced as antagonistic molecules, usually in stress conditions, to compete with closely related bacteria (Michel-Briand and Baysse, 2002;Ghequire and De Mot, 2014).…”

The loss of the pyoverdine secondary receptor inPseudomonas aeruginosaresults in a fitter strain suitable for population invasion

“…The differences can be attributed to the molecular intervention impairing the regulatory network that directly links pyoverdine synthesis and reception, a scenario where ∆fpvB had a selective advantage. Actually, pyoverdine receptors generate a cost to the cells (33) and mutations in FpvB have been detected in clinical isolates obtained from cystic fibrosis patients (34). Our results show that FpvB is generally advantageous under iron limitation, but generates a big cost to the cell in stressful conditions.…”