Human skin commensals augment Staphylococcus aureus pathogenesis

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 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 (PGN), reducing the S. aureus infectious dose by over 1000-fold. This phenomenon occurs using a range of S. aureus strains, 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, KC), that capture and internalise both pathogen and ‘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 initiation of disease by an invading pathogen. As human microflora is ubiquitous2 its role in increasing susceptibility to infection S. aureus highlights potential strategies for disease prevention.