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Niche-specific genome degradation and convergent evolution shaping Staphylococcus aureus adaptation during severe infections

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.7554/eLife.77195

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Role:
Author



Publisher:
eLife Sciences Publications
Journal:
eLife More from this journal
Volume:
11
Article number:
e77195
Publication date:
2022-06-14
Acceptance date:
2022-06-08
DOI:
EISSN:
2050-084X


Language:
English
Keywords:
Pubs id:
1263831
Local pid:
pubs:1263831
Deposit date:
2022-06-15
ARK identifier:

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