Human skin commensals augment Staphylococcus aureus pathogenesis

Emma Boldock, Bas G J Surewaard, Daria Shamarina, Manli Na, Ying Fei, Abukar Ali, Alexander Williams, Eric J G Pollitt, Piotr Szkuta, Paul Morris, Tomasz K Prajsnar, Kathy D McCoy, Tao Jin, David H. Dockrell, Jos A G van Strijp, Paul Kubes, Stephen A Renshaw, Simon J Foster

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)881-890
Number of pages10
JournalNature Microbiology
Volume3
Issue number8
Early online date16 Jul 2018
DOIs
Publication statusPublished - Aug 2018

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