Beschreibung:
<jats:title>ABSTRACT</jats:title><jats:p><jats:italic>Staphylococcus aureus</jats:italic>strains lacking<jats:italic>agr</jats:italic>- and<jats:italic>sarA</jats:italic>-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact<jats:italic>agr</jats:italic>and<jats:italic>sarA</jats:italic>loci were consistently associated with invasive, fatal pulmonary infection (<jats:italic>P</jats:italic>< 0.001) and<jats:italic>sar</jats:italic>A was specifically required to cause bacteremia (<jats:italic>P</jats:italic>< 0.001). The<jats:italic>agr</jats:italic>and/or<jats:italic>sarA</jats:italic>mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast,<jats:italic>agr</jats:italic>and especially<jats:italic>sarA</jats:italic>mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the<jats:italic>agr</jats:italic>and<jats:italic>sarA</jats:italic>loci of<jats:italic>S. aureus</jats:italic>are critical for the coordination of invasive infection of the lungs.</jats:p>