1725. Catheter-associated Staphylococcus aureus biofilms producing staphylococcal enterotoxin B elicit a systemic inflammatory response in the absence of bacteremia
Session: Poster Abstract Session: Studies of the Interface of Host-Microbial Interaction
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
  • IDSA_2013_mice_Jinwon RP_2.pdf (1.4 MB)
  • Background: Catheter-associated S. aureus biofilm infections are significant because of their resistance to antibacterial therapy and persistence. S. aureus can elaborate a variety of superantigens (SAg) which are potent activators of T lymphocytes and other cells of the immune system. SAg contribute to staphylococcal virulence and to the pathogenesis of pneumonia, sepsis and other invasive diseases caused by S. aureus. However, the role of staphylococcal SAg in catheter-associated biofilm infection has not been investigated. We evaluated the local and systemic consequences of catheter-associated SAg-producing and non-producing S. aureus biofilms using C57Bl/6 (B6) and HLA-DR3 transgenic mice; the latter are more responsive to purified SAg than are the former. <>Methods: Biofilms were pre-established on 1 cm-long catheters (14G AbbocathT, Santa Cruz Biotechnology, Inc. Santa Cruz, CA) using isogenic S. aureus strains either producing (SEB+, strain 7419) or not producing (SEB-, strain 7420) staphylococcal enterotoxin B (SEB), both generous gifts from Prof. Richard Novick, NY. Catheters were subcutaneously implanted in age-matched HLA-DR3 and B6 mice. Animals were sacrificed 8 days later. Spleen, thymus and other lymphoid organs were analyzed by flow cytometry. Lung, liver and kidney were collected in buffered formalin for histopathology. Blood and these organs were also collected for culture and the catheters harvested to quantify bacteria.

    Results: HLA-DR3 transgenic mice with SEB+ but not SEB- biofilm catheters had a profound expansion of CD4+ T cells expressing SEB-reactive TCR Vb8 in their spleens and lymph nodes (Figure). Lung, liver and kidney from these mice showed marked inflammatory infiltrates. There was minimal organ pathology and no effect on T cells in B6 mice with either SEB+ or SEB staphylococcal biofilms. All catheter cultures showed bacterial quantities similar to those of pre-inserted catheters (~2.35 x 106 cfu/catheter) and all blood and organ cultures were negative.

    Conclusion: Catheters harboring SEB+ S. aureus biofilms elicited strong systemic immune activation in HLA-DR3 transgenic mice. Thus, SEB and other SAg may play a role in the pathogenesis of biofilm infections in humans.

    Jin-Won Chung, M.D.1, Melissa J. Karau1, Ashenafi Y. Tilahun2, Govindarajan Rajagopalan, Ph.D.2 and Robin Patel, MD, FIDSA, FRCP(C), D(ABMM), FACP, F(AAM)3, (1)Division of Clinical Microbiology, Mayo Clinic, Rochester, MN, (2)Department of Immunology, Mayo Clinic, Rochester, MN, (3)Divisions Of Clinical Microbiology and Infectious Diseases, Mayo Clinic, Rochester, MN


    J. W. Chung, None

    M. J. Karau, None

    A. Y. Tilahun, None

    G. Rajagopalan, None

    R. Patel, Pfizer: Investigator, Research grant
    Pradama : Investigator, Grant recipient
    Astellas: Investigator, Grant recipient
    Tornier: Investigator, Grant recipient
    Pocared: Investigator, Research grant

    Findings in the abstracts are embargoed until 12:01 a.m. PST, Oct. 2nd with the exception of research findings presented at the IDWeek press conferences.