TY - JOUR T1 - On-person adaptive evolution of <em>Staphylococcus aureus</em> during atopic dermatitis increases disease severity JF - bioRxiv DO - 10.1101/2021.03.24.436824 SP - 2021.03.24.436824 AU - Felix M. Key AU - Veda D. Khadka AU - Carolina Romo-González AU - Kimbria J. Blake AU - Liwen Deng AU - Tucker C. Lynn AU - Jean C. Lee AU - Isaac M. Chiu AU - Maria Teresa García-Romero AU - Tami D. Lieberman Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/03/24/2021.03.24.436824.abstract N2 - 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. ER -