Impact of large chromosomal inversions on the adaptation and evolution of Pseudomonas aeruginosa chronically colonizing cystic fibrosis lungs

Abstract

SummaryPseudomonas aeruginosa chronically colonizing the lungs of cystic fibrosis (CF) patients undergoes fast evolution leading to clonal divergence. More than half of the genotypes of P. aeruginosa clone C isolates exclusively from CF lung infection exhibit large chromosomal inversions (LCIs). To analyse the impact of LCIs, as a novel mechanism of bacterial adaptation, the underlying molecular mechanism was examined. Analysis of inversion breakpoints suggested an IS 6100 -induced coupled insertion-inversion mechanism. A selective advantage was created by insertion of IS 6100 into wbpM , pilB and mutS which leads to common CF phenotypes such as O-antigen and type IV pili deficiency and hypermutability. Speciation in bacteria is accompanied by LCIs. Therefore adaptation by LCIs that allows persistence of P. aeruginosa in the CF lung and species diversification in that new ecological niche can serve as a model for bacterial genome evolution.

Sequence diversity of the mucABD locus in Pseudomonas aeruginosa isolates from patients with cystic fibrosis

“…Most information about the evolution of intraclonal diversity of P. aeruginosa has been obtained from retrospective cross-sectional and longitudinal analyses of isolates recovered from the atypical habitat of the lungs of patients with cystic fibrosis (CF) (Ernst et al, 2003;Kresse et al, 2003;Larbig et al, 2002;Smith et al, 2006). A hallmark of The activation of alginate genes is complex (reviewed by Ramsey & Wozniak, 2005).…”

Emergence of phenotypic variants upon mismatch repair disruption in Pseudomonas aeruginosa

“…In recent years, the study of the MMRS in the versatile Pseudomonas aeruginosa (Oliver et al, 2000(Oliver et al, , 2002Pezza et al, 2002a, b;Kresse et al, 2003) revealed that this species constitutes an interesting model to understand the role of this system in bacterial adaptive strategies. The clinical relevance of P. aeruginosa is largely known as it is an important human opportunistic pathogen, frequently involved in severe and often fatal infections in patients with cystic fibrosis (CF) and other immunodepressive illnesses (Govan & Deretic, 1996;van Delden & Iglewski, 1998).…”

Acquisition of multidrug resistance transposon Tn6061 and IS6100-mediated large chromosomal inversions in Pseudomonas aeruginosa clinical isolates

“…An IS6100-mediated chromosomal inversion has been described in SGI1-E, a variant of SGI1 in which floR is disrupted by a duplicated IS6100 (Boyd et al, 2002). Large chromosomal inversions are also associated with IS6100 duplication in P. aeruginosa clinical strains isolated from CF patients (Kresse et al, 2003). These events, by disrupting genes, have been shown to be involved in phenotypic adaptation of the strains to their particular environment (Kresse et al, 2003).…”

“…Large chromosomal inversions are also associated with IS6100 duplication in P. aeruginosa clinical strains isolated from CF patients (Kresse et al, 2003). These events, by disrupting genes, have been shown to be involved in phenotypic adaptation of the strains to their particular environment (Kresse et al, 2003).…”

“…Hypermutator P. aeruginosa with a defective mismatch repair system has been isolated in CF lungs, where the increased mutation frequency may have aided rapid adaptation to this particular niche (Oliver et al, 2000). P. aeruginosa has developed other genetic tools, such as insertion sequence transposition and large chromosomal inversion (Kresse et al, 2003(Kresse et al, , 2006, which, by reorganizing the genome, constitute adaptive mechan-isms. Horizontal gene transfer, a common feature in P. aeruginosa, confers new functions by the acquisition of plasmids, transposons or pathogenicity islands.…”