RT Journal Article SR Electronic T1 On-person adaptive evolution of Staphylococcus aureus during atopic dermatitis increases disease severity JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.24.436824 DO 10.1101/2021.03.24.436824 A1 Felix M. Key A1 Veda D. Khadka A1 Carolina Romo-González A1 Kimbria J. Blake A1 Liwen Deng A1 Tucker C. Lynn A1 Jean C. Lee A1 Isaac M. Chiu A1 Maria Teresa García-Romero A1 Tami D. Lieberman YR 2021 UL http://biorxiv.org/content/early/2021/03/24/2021.03.24.436824.abstract AB Bacteria acquire adaptive mutations during infections and within healthy microbiomes 1-4, but the potential of bacterial mutations to impact disease is not well understood. The inflamed skin of people with atopic dermatitis (AD) is heavily colonized with Staphylococcus aureus, an opportunistic pathogen associated with both asymptomatic colonization of nasal passages and invasive disease5,6. While host genetic risk is critical to AD initiation 7,8, S. aureus worsens disease severity by inducing skin damage9. Here, we longitudinally track S. aureus evolution on 25 children with AD over 9 months —sequencing the genomes of 1,330 colonies— and identify common adaptive de novo mutations that exacerbate skin disease in vivo. Novel S. aureus genotypes replace their ancestors across the body within months, with signatures of adaptive, rather than neutral, forces. Most strikingly, the capsule synthesis gene capD obtained four parallel mutations within one patient and is involved in mutational sweeps in multiple patients. Despite the known role of capsule in phagocytic evasion10, we find that an acapsular ΔcapD strain colonizes better and produces worse disease severity on mouse skin than its encapsulated parental strain. Moreover, re-analysis of publicly available S. aureus genomes from 276 people confirms that CapD truncations are significantly more common among strains isolated from AD patients relative to other contexts. Together, these results suggest that targeting capsule-negative strains may be a potential avenue for decreasing S. aureus skin colonization and highlight the importance of single-mutation resolution for characterizing microbe-disease associations.Competing Interest StatementThe authors have declared no competing interest.