Severe infections emerge from commensal bacteria by adaptive evolution

Young, Bernadette C, Wu, Chieh-Hsi, Gordon, N Claire, Cole, Kevin, Price, James R, Liu, Elian, Sheppard, Anna E, Perera, Sanuki, Charlesworth, Jane, Golubchik, Tanya, Iqbal, Zamin, Bowden, Rory, Massey, Ruth C, Paul, John, Crook, Derrick W, Peto, Timothy E, Walker, A Sarah, Llewelyn, Martin J, Wyllie, David H and Wilson, Daniel J (2017) Severe infections emerge from commensal bacteria by adaptive evolution. eLife, 6. e30637. ISSN 2050-084X

[img] PDF - Published Version
Available under License Creative Commons Attribution.

Download (832kB)

Abstract

Bacteria responsible for the greatest global mortality colonize the human microbiota far more frequently than they cause severe infections. Whether mutation and selection among commensal bacteria are associated with infection is unknown. We investigated de novo mutation in 1163 Staphylococcus aureus genomes from 105 infected patients with nose colonization. We report that 72% of infections emerged from the nose, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold adaptive enrichments of protein-altering variants in genes responding to rsp, which regulates surface antigens and toxin production; agr, which regulates quorum-sensing, toxin production and abscess formation; and host-derived antimicrobial peptides. Adaptive mutations in pathogenesis-associated genes were 3.1-fold enriched in infecting but not nose-colonizing bacteria. None of these signatures were observed in healthy carriers nor at the species-level, suggesting infection-associated, short-term, within-host selection pressures. Our results show that signatures of spontaneous adaptive evolution are specifically associated with infection, raising new possibilities for diagnosis and treatment.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Global Health and Infection
Subjects: R Medicine
R Medicine > R Medicine (General)
Depositing User: Sandy Gray
Date Deposited: 15 Jan 2018 14:13
Last Modified: 15 Jan 2018 14:13
URI: http://sro.sussex.ac.uk/id/eprint/72826

View download statistics for this item

📧 Request an update