Vancomycin intermediate strains of Staphylococcus aureus have dampened induction of type I interferon production

Abstract

Abstract Studies by our group have shown that interferon (IFN) signaling contributes to pathogenesis of Staphylococcus aureus pneumonia and that different strains of S. aureus can activate type I IFN signaling via distinct receptors, such as TLR9 and NOD2, at various amplitudes. In this study we investigated the capacity of a wide range of S. aureus strains to induce both type I & III IFN. We screened 78 S. aureus strains from various clinical scenarios for their ability to induce IFN-β and IFN-λ in bone marrow-derived dendritic cells (BMDC) and found that both cytokines are differentially induced by various S. aureus strains independently of their isolation sites or methicillin resistance profiles. These induction patterns persisted over time and type I & III IFN differentially correlated with tumor necrosis factor α (TNF-α) production. Furthermore, vancomycin intermediate S. aureus (VISA) strains induced up to 45-fold less (P<0.001) IFN-β than the current epidemic methicillin-resistant S. aureus strain USA300 and displayed increased in vitro survival (up to 9-fold) after 4-hour exposure to BMDC. Further investigation of one VISA strain, HIP07930, showed decreased autolysis and increased resistance to lysostaphin compared to USA300, consistent with its reduction in IFN β induction. Interestingly, this strain also displayed decreased in vivo virulence compared to USA300 in a murine acute pneumonia model of infection (4.9-fold and 54.5-fold decrease in colony forming units in bronchoalveolar lavage fluid and lung homogenates, respectively, 24 hours post infection). Overall, this study demonstrates the heterogeneity of IFN induction by S. aureus and uncovered a unique property of VISA strains in their inability to induce type I IFN production.