Document Type
Article
Publication Date
1-2002
Publication Title
Infection and Immunity
Department
Geisel School of Medicine
Abstract
Staphylococcus aureus strains lacking agr- and sarA-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 agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA 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, agr and especially sarA 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 agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.
DOI
10.1128/IAI.70.1.127-133.2002
Original Citation
Heyer G, Saba S, Adamo R, et al. Staphylococcus aureus agr and sarA functions are required for invasive infection but not inflammatory responses in the lung. Infect Immun. 2002;70(1):127-133. doi:10.1128/iai.70.1.127-133.2002
Dartmouth Digital Commons Citation
Heyer, Geoffrey; Saba, Shahryar; Adamo, Robert; Rush, William; Soong, Grace; Cheung, Ambrose; and Prince, Alice, "Staphylococcus aureus agr and sarA Functions Are Required for Invasive Infection but Not Inflammatory Responses in the Lung" (2002). Dartmouth Scholarship. 966.
https://digitalcommons.dartmouth.edu/facoa/966
Included in
Infectious Disease Commons, Medical Microbiology Commons, Medical Pathology Commons, Respiratory System Commons
