Severe infections emerge from commensal bacteria by adaptive evolution

Bernadette C Young, Chieh-Hsi Wu, N Claire Gordon, Kevin Cole, James R Price, Elian Liu, Anna E Sheppard, Sanuki Perera, Jane Charlesworth, Tanya Golubchik, Zamin Iqbal, Rory Bowden, Ruth C Massey, John Paul, Derrick W Crook, Timothy E Peto, A Sarah Walker, Martin J Llewelyn, David H Wyllie, Daniel J Wilson

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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.

Original languageEnglish
Article numbere30637
Number of pages25
JournaleLife
Volume6
DOIs
Publication statusPublished - 19 Dec 2017

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