Whole genome sequencing reveals the emergence of a<i>Pseudomonas aeruginosa</i>shared strain sub-lineage among patients treated within a single cystic fibrosis centre

Wee, Bryan A.; Tai, Anna; Sherrard, L.; Zakour, Nouri L. Ben; Hanks, Kirt R; Kidd, Timothy J.; Ramsay, Kay A.; Lamont, Iain L.; Whiley, David M.; Bell, S. C.; Beatson, Scott A.

doi:10.1101/261586

Cited by 2 publications

(3 citation statements)

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“…It has previously hypothesized that virulence factors are selected against in CF infections, and in agreement with this we found that 34 of the 52 highly variable genes were lost as part of a genomic region encoding virulence factors hydrogen cyanide synthase (hcnABC) and type III secreted protein ExoY (exoY). It has also been shown by Wee et al (2018) [31] that selective pressures for losing hcnA, hcnB, hcnC and exoY genes exist, and we notice that Wee et al…”

Section: Convergent Evolution and Adaptive Loss Of Virulencesupporting

confidence: 61%

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Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Gabrielaitė

Molin

et al. 2020

Preprint

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While genome analyses have documented that there are differences in the gene repertoire between evolutionary distant lineages of the same bacterial species, less is known about micro-evolutionary dynamics of gene loss and acquisition within lineages of bacteria as they evolve over the timescale of years. This knowledge is valuable to understand both the basic mutational steps that on long timescales lead to evolutionary distant bacterial lineages, and the evolution of the individual lineages themselves.In the case that lineages evolve in a human host environment, gene loss and acquisition may furthermore have implication for disease.We analyzed the genomes of 45 Pseudomonas aeruginosa lineages evolving in the lungs of cystic fibrosis patients to identify genes that are lost or acquired during the first years of infection in each of the different lineages. On average, the lineage genome content changed with 88 genes (range 0-473). Genes were more often lost than acquired, and prophage genes were more variable than bacterial genes. We identified genes that were lost or acquired independently across different clonal lineages, i.e. convergent molecular evolution. Convergent evolution suggests that there is a selection for loss and acquisition of certain genes in the host environment. We find that a significant proportion of such genes are associated with virulence; a trait previously shown to be important for adaptation. Furthermore, we also compared the genomes across lineages to show that within-lineage variable genes more often belonged to genomic content not shared across all lineages. Finally, we used 4,760 genes shared by 446 P. aeruginosa genomes to develop a stable and discriminatory typing scheme for P. aeruginosa clone types (Pactyper, https://github.com/MigleSur/Pactyper). In sum, our analysis adds to the knowledge on the pace and drivers of gene loss and acquisition in bacteria evolving over multiple years in a human host environment 3 and provides a basis to further understand how gene loss and acquisition plays a role in lineage differentiation and host adaptation.

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Section: Convergent Evolution and Adaptive Loss Of Virulencesupporting

confidence: 61%

“…Literature search identified that four of the genes (hcnABC and exoY encoding hydrogen cyanide synthase and type III secreted protein, respectively) are known to play a role in virulence and pathogenesis of P. aeruginosa. [30,31]…”

Section: Convergent Evolution Of Locus With Hcnabc and Exoy Genesmentioning

confidence: 99%

Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Gabrielaitė

Molin

et al. 2020

Preprint

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“…Chronic infection of CF lungs with highly adapted and antibiotic resistant biofilms of P. aeruginosa is a major cause of lung function decline, which results in a concomitant increase in morbidity and mortality in individuals with CF (3,4,(6)(7)(8)(9)(10)(11). Longitudinal studies of chronic CF infections with P. aeruginosa have revealed that patients become infected at a young age with an environmental or transmissible isolate that evolves and adapts over time to the lung environment (12)(13)(14)(15)(16)(17)(18). Studies on P. aeruginosa populations isolated from individual lungs, have demonstrated divergent evolution, resulting in heterogeneous populations of P. aeruginosa within patients (16,17,19).…”

Section: Introductionmentioning

confidence: 99%

Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations

Azimi

Roberts

Peng

et al. 2019

Preprint

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AbstractPseudomonas aeruginosa is an opportunistic pathogen that chronically infects the lungs of individuals with cystic fibrosis (CF) by forming antibiotic resistant biofilms. Emergence of phenotypically diverse isolates within CF P. aeruginosa populations has previously been reported, however, the impact of heterogeneity on social behaviors and community function is poorly understood. Here we describe how this heterogeneity impacts on behavioral traits by evolving the strain PAO1 in biofilms grown in a synthetic sputum medium for 50 days. We measured social trait production and antibiotic tolerance and used a metagenomic approach to analyze and assess genomic changes over the duration of the evolution experiment. We found that (i) evolutionary trajectories were reproducible in independently evolving populations; (ii) over 60% of genomic diversity occurred within the first 10 days of selection. We then focused on quorum sensing (QS), a well-studied P. aeruginosa trait that is commonly mutated in strains isolated from CF lungs. We found that at the population level (i) evolution in sputum medium selected for decreased production of QS and QS-dependent traits; (ii) there was a significant correlation between lasR mutant frequency, the loss of protease and the 3O-C12-HSL signal, and an increase in resistance to clinically relevant β-lactam antibiotics, despite no previous antibiotic exposure. Overall, our findings provide insights into the effect of allelic polymorphism on community functions in diverse P. aeruginosa populations. Further, we demonstrate that P. aeruginosa population and evolutionary dynamics can impact on traits important for virulence and can lead to increased tolerance to β-lactam antibiotics.

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Whole genome sequencing reveals the emergence of aPseudomonas aeruginosashared strain sub-lineage among patients treated within a single cystic fibrosis centre

Cited by 2 publications

References 59 publications

Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Gene loss and acquisition in lineages of bacteria evolving in a human host environment

Allelic polymorphism shapes community function in evolving Pseudomonas aeruginosa populations

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