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Nat Microbiol. 2018 Aug;3(8):881-890. doi: 10.1038/s41564-018-0198-3. Epub 2018 Jul 16.

Human skin commensals augment Staphylococcus aureus pathogenesis.

Author information

1
Florey Institute, University of Sheffield, Sheffield, UK.
2
Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK.
3
Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
4
Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Canada.
5
Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands.
6
Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
7
Department of Microbiology and Immunology, The Affiliated Hospital of GuiZhou Medical University, GuiZhou Sheng, China.
8
Bateson Centre, University of Sheffield, Sheffield, UK.
9
Western Canadian Microbiome Centre, Cumming School of Medicine, University of Calgary, Calgary, Canada.
10
Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden.
11
MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
12
Florey Institute, University of Sheffield, Sheffield, UK. S.Foster@sheffield.ac.uk.
13
Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, UK. S.Foster@sheffield.ac.uk.

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.

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PMID:
30013237
PMCID:
PMC6207346
DOI:
10.1038/s41564-018-0198-3
[Indexed for MEDLINE]
Free PMC Article

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