Boldock, E. orcid.org/0000-0001-7150-7990, Surewaard, B.G.J., Shamarina, D. et al. (15 more authors) (2018) Human skin commensals augment Staphylococcus aureus pathogenesis. Nature Microbiology, 3 (8). pp. 881-890. ISSN 2058-5276
Abstract
All bacterial infections occur within a polymicrobial environment, from which a pathogen population emerges to establish disease within a host. Emphasis has been placed on prevention of pathogen dominance by competing microflora acting as probiotics1. Here we show that the virulence of the human pathogen Staphylococcus aureus is augmented by native, polymicrobial, commensal skin flora and individual species acting as ‘proinfectious agents’. The outcome is pathogen proliferation, but not commensal. Pathogenesis augmentation can be mediated by particulate cell wall peptidoglycan, reducing the S. aureus infectious dose by over 1,000-fold. This phenomenon occurs using a range of S. aureus strains and infection models and is not mediated by established receptor-mediated pathways including Nod1, Nod2, Myd88 and the NLPR3 inflammasome. During mouse sepsis, augmentation depends on liver-resident macrophages (Kupffer cells) that capture and internalize both the pathogen and the proinfectious agent, leading to reduced production of reactive oxygen species, pathogen survival and subsequent multiple liver abscess formation. The augmented infection model more closely resembles the natural situation and establishes the role of resident environmental microflora in the initiation of disease by an invading pathogen. As the human microflora is ubiquitous2, its role in increasing susceptibility to infection by S. aureus highlights potential strategies for disease prevention.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 The Authors. This is an author produced version of a paper subsequently published in Nature Microbiology. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number WELLCOME TRUST (THE) 099957/Z/12/Z MEDICAL RESEARCH COUNCIL MR/R001111/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 12 Oct 2018 09:44 |
Last Modified: | 13 Jan 2020 10:48 |
Published Version: | https://doi.org/10.1038/s41564-018-0198-3 |
Status: | Published |
Publisher: | Nature Research |
Refereed: | Yes |
Identification Number: | 10.1038/s41564-018-0198-3 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:137012 |