Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection

Article English OPEN
Darch, Sophie E. ; McNally, Alan ; Harrison, Freya ; Corander, Jukka ; Barr, Helen L. ; Paszkiewicz, Konrad ; Holden, Stephen ; Fogarty, Andrew ; Crusz, Shanika A. ; Diggle, Stephen P. (2015)
  • Publisher: Nature Publishing Group
  • Journal: Scientific Reports (vol: 5)
  • Related identifiers: doi: 10.1038/srep07649, pmc: PMC4289893
  • Subject: EPIDEMIC STRAIN | 1183 Plant biology, microbiology, virology | TRANSMISSION | BACTERIAL GENOMES | TUBERCULOSIS | ESCHERICHIA-COLI | N-ACYLHOMOSERINE LACTONES | EVOLUTION | LUNG INFECTIONS | INDIVIDUALS | Article | SPREAD

The Cystic Fibrosis (CF) lung harbors a complex, polymicrobial ecosystem, in which Pseudomonas aeruginosa is capable of sustaining chronic infections, which are highly resistant to multiple antibiotics. Here, we investigate the phenotypic and genotypic diversity of 44 morphologically identical P. aeruginosa isolates taken from a single CF patient sputum sample. Comprehensive phenotypic analysis of isolates revealed large variances and trade-offs in growth, virulence factors and quorum sensing (QS) signals. Whole genome analysis of 22 isolates revealed high levels of intra-isolate diversity ranging from 5 to 64 SNPs and that recombination and not spontaneous mutation was the dominant driver of diversity in this population. Furthermore, phenotypic differences between isolates were not linked to mutations in known genes but were statistically associated with distinct recombination events. We also assessed antibiotic susceptibility of all isolates. Resistance to antibiotics significantly increased when multiple isolates were mixed together. Our results highlight the significant role of recombination in generating phenotypic and genetic diversification during in vivo chronic CF infection. We also discuss (i) how these findings could influence how patient-to-patient transmission studies are performed using whole genome sequencing, and (ii) the need to refine antibiotic susceptibility testing in sputum samples taken from patients with CF.
  • References (67)
    67 references, page 1 of 7

    1. Sadikot, R. T., Blackwell, T. S., Christman, J. W. & Prince, A. S. Pathogen-host interactions in Pseudomonas aeruginosa pneumonia. Am. J. Res. Care Med. 171, 1209-1223 (2005).

    2. Govan, J. R. & Deretic, V. Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia. Microbiol. Rev. 60, 539-574 (1996).

    3. Hart, C. A. & Winstanley, C. Persistent and aggressive bacteria in the lungs of cystic fibrosis children. Brit. Med. Bull. 61, 81-96 (2002).

    4. Goss, C. H., Mayer-Hamblett, N., Kronmal, R. A., Williams, J. & Ramsey, B. W. Laboratory parameter profiles among patients with cystic fibrosis. J. Cyst. Fibro. 6, 117-123 (2007).

    5. Fothergill, J. L. et al. Widespread pyocyanin over-production among isolates of a cystic fibrosis epidemic strain. BMC Microbiol. 7, 45 (2007).

    6. Fothergill, J. L., Walshaw, M. J. & Winstanley, C. Transmissible strains of Pseudomonas aeruginosa in cystic fibrosis lung infections. Euro. Resp. J. 40, 227-238 (2012).

    7. Jones, A. M. et al. Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic. Lancet 358, 557-558 (2001).

    8. Bragonzi, A. et al. Pseudomonas aeruginosa microevolution during cystic fibrosis lung infection establishes clones with adapted virulence. Am. J. Res. Crit. Care Med. 180, 138-145 (2009).

    9. Mowat, E. et al. Pseudomonas aeruginosa population diversity and turnover in cystic fibrosis chronic infections. Am. J. Res. Crit. Care Med. 183, 1674-1679 (2011).

    10. Smith, E. E. et al. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 103, 8487-8492 (2006).

  • Related Research Results (2)
  • Metrics
    No metrics available
Share - Bookmark