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

Research output: Contribution to journalArticle

Authors

  • Sophie E Darch
  • Freya Harrison
  • Jukka Corander
  • Helen L Barr
  • Konrad Paszkiewicz
  • Stephen Holden
  • Andrew Fogarty
  • Shanika A Crusz
  • Stephen P Diggle

Colleges, School and Institutes

Abstract

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.

Details

Original languageEnglish
Pages (from-to)7649
JournalScientific Reports
Volume5
Publication statusPublished - 2015

Keywords

  • Anti-Bacterial Agents, Cystic Fibrosis, Drug Resistance, Microbial, Evolution, Molecular, Female, Genetic Variation, Genome, Bacterial, Genotype, Genotyping Techniques, Humans, Microbial Sensitivity Tests, Mutation, Phenotype, Phylogeny, Polymorphism, Single Nucleotide, Pseudomonas Infections, Pseudomonas aeruginosa, Quorum Sensing, Recombination, Genetic, Sequence Alignment, Sputum, Young Adult