These papers have been, or are about to be, submitted for peer review.Severe infections emerge from the microbiome by adaptive evolution
Young, B. C., Wu, C.-H., Gordon, N. C., Cole, K., Price, J. R., Lui, E., Sheppard, A. E., Perera, S., Charlesworth, J., Golubchik, T., Iqbal, Z., Bowden, R., Massey, R. C., Paul, J., Crook, D. W., Peto, T. E. A., Walker, A. S., Llewelyn, M. J., Wyllie, D. H. and D. J. Wilson (2017)
biorxiv doi:10.1101/116681 (preprint)
Bacteria responsible for the greatest global mortality colonize the human microbiome far more frequently than they cause severe infections. Whether mutation and selection within the microbiome accompany 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 microbiome, with infecting and nose-colonizing bacteria showing parallel adaptive differences. We found 2.8-to-3.6-fold enrichments of protein-altering variants in genes responding to rsp, which regulates surface antigens and toxicity; agr, which regulates quorum-sensing, toxicity 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 disease-associated, short-term, within-host selection pressures. Our results show that infection, like a cancer of the microbiome, emerges through spontaneous adaptive evolution, raising new possibilities for diagnosis and treatment.