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

Author:

Giulieri Stefano G123,Guérillot Romain1,Duchene Sebastian1,Hachani Abderrahman1ORCID,Daniel Diane14,Seemann Torsten4,Davis Joshua S56,Tong Steven YC67ORCID,Young Bernadette C8ORCID,Wilson Daniel J9ORCID,Stinear Timothy P1ORCID,Howden Benjamin P124ORCID

Affiliation:

1. Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne

2. Department of Infectious Diseases, Austin Health

3. Victorian Infectious Diseases Service, Royal Melbourne Hospital

4. Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne at the Doherty Institute for Infection and Immunity

5. Department of Infectious Diseases, John Hunter Hospital

6. Menzies School of Health Research, Charles Darwin University

7. Victorian Infectious Disease Service, Royal Melbourne Hospital, and University of Melbourne at the Peter Doherty Institute for Infection and Immunity

8. Nuffield Department of medicine

9. Big Data Institute, Nuffield Department of Population Health, Li Ka Shing Centre for Health Information and Discovery, Old Road Campus, University of Oxford

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 2590 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.

Funder

National Health and Medical Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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