Niche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections
- University of Melbourne, Australia
- John Hunter Hospital, Australia
- University of Oxford, United Kingdom
Abstract
During severe infections, Staphylococcus aureus moves from its colonising sites to blood and tissues, and is exposed to new selective pressures, thus potentially driving adaptive evolution. Previous studies have shown the key role of the agr locus in S. aureus pathoadaptation, however a more comprehensive characterisation of genetic signatures of bacterial adaptation may enable prediction of clinical outcomes and reveal new targets for treatment and prevention of these infections. Here, we measured adaptation using within-host evolution analysis of 2,590 S. aureus genomes from 396 independent episodes of infection. By capturing a comprehensive repertoire of single-nucleotide and structural genome variations, we found evidence of a distinctive evolutionary pattern within the infecting populations compared to colonising bacteria. These invasive strains had up to 20-fold enrichments for genome degradation signatures and displayed significantly convergent mutations in a distinctive set of genes, linked to antibiotic response and pathogenesis. In addition to agr-mediated adaptation we identified non-canonical, genome-wide significant loci including sucA-sucB and stp1. The prevalence of adaptive changes increased with infection extent, emphasising the clinical significance of these signatures. These findings provide a high-resolution picture of the molecular changes when S. aureus transitions from colonisation to severe infection and may inform correlation of infection outcomes with adaptation signatures.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting file 1-6.The code to call, filter and annotated within-host variants and to perform the enrichment analysis is available on github at https://github.com/stefanogg/staph_adaptation_paper
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Article and author information
Author details
Abderrahman Hachani
Bernadette C Young
Funding
National Health and Medical Research Council
- Timothy P Stinear
National Health and Medical Research Council
- Benjamin P Howden
The University of Melbourne
- Stefano G Giulieri
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Bavesh D Kana, University of the Witwatersrand, South Africa
Ethics
Human subjects: Ethics approval was obtained at each partecipating site to the CAMERA2 trial and written informed onsent was obtained from each participant or surrogate decision maker.
Version history
- Received: January 19, 2022
- Preprint posted: February 12, 2022 (view preprint)
- Accepted: June 8, 2022
- Accepted Manuscript published: June 14, 2022 (version 1)
- Version of Record published: July 8, 2022 (version 2)
Copyright
© 2022, Giulieri et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Niche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections
eLife 11:e77195.
https://doi.org/10.7554/eLife.77195
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