Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection
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. ae...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2015
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| Online Access: | https://eprints.nottingham.ac.uk/31951/ |
| _version_ | 1848794303798706176 |
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| author | Darch, Sophie E. McNally, Alan Harrison, Freya Corander, Jukka Barr, Helen L. Paszkiewicz, Konrad Holden, Stephen Fogarty, Andrew W. Crusz, Shanika A. Diggle, Stephen P. |
| author_facet | Darch, Sophie E. McNally, Alan Harrison, Freya Corander, Jukka Barr, Helen L. Paszkiewicz, Konrad Holden, Stephen Fogarty, Andrew W. Crusz, Shanika A. Diggle, Stephen P. |
| author_sort | Darch, Sophie E. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:14:03Z |
| format | Article |
| id | nottingham-31951 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:14:03Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-319512020-05-04T17:01:07Z https://eprints.nottingham.ac.uk/31951/ Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection Darch, Sophie E. McNally, Alan Harrison, Freya Corander, Jukka Barr, Helen L. Paszkiewicz, Konrad Holden, Stephen Fogarty, Andrew W. Crusz, Shanika A. Diggle, Stephen P. 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. Nature Publishing Group 2015-01-12 Article PeerReviewed Darch, Sophie E., McNally, Alan, Harrison, Freya, Corander, Jukka, Barr, Helen L., Paszkiewicz, Konrad, Holden, Stephen, Fogarty, Andrew W., Crusz, Shanika A. and Diggle, Stephen P. (2015) Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection. Scientific Reports, 5 . 7649/1-7649/12. ISSN 2045-2322 http://www.nature.com/articles/srep07649 doi:10.1038/srep07649 doi:10.1038/srep07649 |
| spellingShingle | Darch, Sophie E. McNally, Alan Harrison, Freya Corander, Jukka Barr, Helen L. Paszkiewicz, Konrad Holden, Stephen Fogarty, Andrew W. Crusz, Shanika A. Diggle, Stephen P. Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection |
| title | Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection |
| title_full | Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection |
| title_fullStr | Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection |
| title_full_unstemmed | Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection |
| title_short | Recombination is a key driver of genomic and phenotypic diversity in a Pseudomonas aeruginosa population during cystic fibrosis infection |
| title_sort | recombination is a key driver of genomic and phenotypic diversity in a pseudomonas aeruginosa population during cystic fibrosis infection |
| url | https://eprints.nottingham.ac.uk/31951/ https://eprints.nottingham.ac.uk/31951/ https://eprints.nottingham.ac.uk/31951/ |