Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species

Author summaryS. aureus is a commensal inhabitant of the human skin and nares. However, it can cause serious diseases if it is able to breach our protective barriers such as the skin, often via wounds or surgery. If infection occurs via a wound, this initial inoculum contains both the pathogen, other members of the microflora and also wider environmental microbes. We have previously described "augmentation", whereby this other non-pathogenic material can enhance the ability of S. aureus to lead to a serious disease outcome. Here we have determined the breadth of augmenting material and elucidated the cellular and molecular basis for its activity. Augmentation occurs via shielding of S. aureus from the direct bactericidal effects of reactive oxygen species produced by macrophages. This initial protection enables the effective establishment of S. aureus infection. Understanding augmentation not only explains an important facet of the interaction of S. aureus with our innate immune system, but also provides a platform for the development of novel prophylaxis approaches. 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.