On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis

Felix M Key; Veda D Khadka; Carolina Romo-González; Kimbria J Blake; Liwen Deng; Tucker C Lynn; Jean C Lee; Isaac M Chiu; Maria T García-Romero; Tami D Lieberman

doi:10.1016/j.chom.2023.03.009

On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis

Cell Host Microbe. 2023 Apr 12;31(4):593-603.e7. doi: 10.1016/j.chom.2023.03.009.

Authors

Affiliations

¹ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
² Experimental Bacteriology Laboratory, National Institute for Pediatrics, Mexico City, Mexico.
³ Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
⁴ Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
⁵ Department of Dermatology, National Institute for Pediatrics, Mexico City, Mexico. Electronic address: mgarciar@pediatria.gob.mx.
⁶ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Civil and Environmental Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Broad Institute, Massachusetts Institute of Technology, Cambridge, MA, USA; Ragon Institute, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: tami@mit.edu.

Abstract

The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus population is dominated by a single lineage, with infrequent invasion by distant lineages. Mutations emerge within each lineage at rates similar to those of S. aureus in other contexts. Some variants spread across the body within months, with signatures of adaptive evolution. Most strikingly, mutations in capsule synthesis gene capD underwent parallel evolution in one patient and across-body sweeps in two patients. We confirm that capD negativity is more common in AD than in other contexts, via reanalysis of S. aureus genomes from 276 people. Together, these findings highlight the importance of the mutation level when dissecting the role of microbes in complex disease.

Keywords: Staphylococcus aureus; atopic dermatitis; capsule; eczema; genomics; microevolution; natural selection; skin infection; skin microbiome; within-person evolution.

MeSH terms

Child
Dermatitis, Atopic*
Humans
Mutation
Skin
Staphylococcal Infections*
Staphylococcus aureus / genetics

Abstract

MeSH terms

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