• Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection.

      Tuchscherr, Lorena; Medina, Eva; Hussain, Muzaffar; Völker, Wolfgang; Heitmann, Vanessa; Niemann, Silke; Holzinger, Dirk; Roth, Johannes; Proctor, Richard A; Becker, Karsten; et al. (2011-03)
      Staphylococcus aureus is a frequent cause for serious, chronic and therapy-refractive infections in spite of susceptibility to antibiotics in vitro. In chronic infections, altered bacterial phenotypes, such as small colony variants (SCVs), have been found. Yet, it is largely unclear whether the ability to interconvert from the wild-type to the SCV phenotype is only a rare clinical and/or just laboratory phenomenon or is essential to sustain an infection. Here, we performed different long-term in vitro and in vivo infection models with S. aureus and we show that viable bacteria can persist within host cells and/or tissues for several weeks. Persistence induced bacterial phenotypic diversity, including SCV phenotypes, accompanied by changes in virulence factor expression and auxotrophism. However, the recovered SCV phenotypes were highly dynamic and rapidly reverted to the fully virulent wild-type form when leaving the intracellular location and infecting new cells. Our findings demonstrate that bacterial phenotype switching is an integral part of the infection process that enables the bacteria to hide inside host cells, which can be a reservoir for chronic and therapy-refractive infections.
    • Subcutaneous infection with S. aureus in mice reveals association of resistance with influx of neutrophils and Th2 response.

      Nippe, Nadine; Varga, Georg; Holzinger, Dirk; Löffler, Bettina; Medina, Eva; Becker, Karsten; Roth, Johannes; Ehrchen, Jan M; Sunderkötter, Cord; Institute of Immunology, University of Muenster, Muenster, Germany. (2011-01)
      Staphylococcus aureus is the leading cause of bacterial skin infection. Once it overcomes the epithelial barrier, it either remains locally controlled or spreads in the dermis causing soft tissue infection. These different courses depend not only on its virulence factors, but also on the immune response of the infected individual. The goal of this study was to identify host factors that influence different outcomes. We, therefore, established comparative analysis of subcutaneous footpad infection with S. aureus (SH1000) in different inbred mouse strains. We found that C57BL/6 mice are more susceptible than BALB/c and DBA/2 mice, reflected by significantly higher footpad swelling and bacterial load, as well as increased dissemination of bacteria into inguinal lymph nodes and kidneys. This susceptibility was associated with lower influx of polymorphonuclear leukocytes (PMNs), but higher secretion of CXCL-2. Remarkably, resistance correlated with S. aureus-specific Th2-cell response in BALB/c and DBA/2 mice, whereas susceptible C57BL/6 mice generated a Th1-cell response. As Th1 cells are able to induce release of CXCL-2, and as CXCL-2 is able to increase the survival of S. aureus within PMNs, interactions between PMNs and Th1 or Th2 cells need to be considered as important mechanisms of resistance in murine soft tissue infection with S. aureus.