Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species
2021
Gibson, Josie | Pidwill, Grace | Carnell, Oliver | Surewaard, Bas | Shamarina, Daria | Sutton, Joshua | Jeffery, Charlotte | Derré-Bobillot, Aurélie | Archambaud, Cristel | Siggins, Matthew | Pollitt, Eric | Johnston, Simon | Serror, Pascale | Sriskandan, Shiranee | Renshaw, Stephen | Foster, Simon | University of Sheffield [Sheffield] | University of Calgary | MICrobiologie de l'ALImentation au Service de la Santé (MICALIS) ; AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Imperial College London | SAR and SJF were supported by Medical Research Council (MRC) grant MR/R001111/1 (www.mrc.ukri.org), SAJ was supported by MRC grant MR/J009156/1 (www.mrc.ukri.org), and SS by MRC grant MR/L008610/1 (www.mrc.ukri.org).PS were supported by the French National Research Institute for Agriculture, Food, and Environment (INRAE) funding (www.inrae.fr).Imaging was performed in the Sheffield RNAi Screening Facility (Wellcome Trust grant reference number 084757 (www.wellcome.org)) and the Wolfson Light Microscopy Facility (MRC grant G0700091 (www.mrc.ukri.org) and Wellcome grant 077544/Z/05/Z (www.wellcome.org)).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Show more [+] Less [-]English. Staphylococcus aureus is a human commensal organism and opportunist pathogen, causing potentially fatal disease. The presence of non-pathogenic microflora or their components, at the point of infection, dramatically increases S . aureus pathogenicity, a process termed augmentation. Augmentation is associated with macrophage interaction but by a hitherto unknown mechanism. Here, we demonstrate a breadth of cross-kingdom microorganisms can augment S . aureus disease and that pathogenesis of Enterococcus faecalis can also be augmented. Co-administration of augmenting material also forms an efficacious vaccine model for S . aureus . In vitro , augmenting material protects S . aureus directly from reactive oxygen species (ROS), which correlates with in vivo studies where augmentation restores full virulence to the ROS-susceptible, attenuated mutant katA ahpC . At the cellular level, augmentation increases bacterial survival within macrophages via amelioration of ROS, leading to proliferation and escape. We have defined the molecular basis for augmentation that represents an important aspect of the initiation of infection.
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