251 EMF Inadequate Immune Response to Staphylococcus Aureus in Complicated Abscess Infections

Abstract

Abscess infections frequently present to the emergency department (ED) and are an opportunity to determine the molecular factors that contribute to disease severity. The goal of this work was to determine the concentration of host immune mediators including IFN-γ, IL-17, IL-1β, and TNF-α and apolipoprotein B (apoB) in complicated and simple infections caused by Staphylococcus aureus. We hypothesized that complicated infections would have deficiencies in local host immunity and enhanced bacterial virulence. To test this hypothesis we measured both host proteins and bacterial virulence gene expression in complicated and simple abscesses. We obtained abscess fluid from subjects presenting to the ED with simple and complicated infections as defined by current clinical guidelines. We then performed multiplex protein analysis on collected abscess fluids and patient serum samples. In addition, we examined S. aureus virulence gene expression by quantitative-PCR. We found differences in cytokine profiles with complicated abscesses having altered IFN-γ, IL-17, IL-1β, TNF-α, and IL-10 responses when compared to simple abscesses. We found that apoB, which disrupts bacterial quorum sensing, was lower in complicated infections. In addition to differences in the local inflammatory responses, several bacterial virulence genes were upregulated in complicated infections. These genes include bacterial toxins and bacterial stress response genes. Together these findings translate clinical findings of disease severity into molecular determinants of pathogenesis and reveal a potential mechanism by which future antimicrobials could enhance treatment. Specifically, these data identify local host defects in inflammation and control of bacterial communication. These defects are associated with increases in bacterial virulence gene expression and reveal a potential role for quorum sensing inhibitors as a way of augmenting defective host immunity.