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Infection and Immunity, January 2002, p. 127-133, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.127-133.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Staphylococcus aureus agr and sarA Functions Are Required for Invasive Infection but Not Inflammatory Responses in the Lung

Geoffrey Heyer,1 Shahryar Saba,1 Robert Adamo,1 William Rush,1 Grace Soong,1 Ambrose Cheung,2 and Alice Prince1*

Columbia University College of Physicians and Surgeons, New York, New York,1 Dartmouth Medical School, Hanover, New Hampshire2

Received 15 August 2001/ Returned for modification 25 September 2001/ Accepted 16 October 2001

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.

* Corresponding author. Mailing address: Department of Pediatrics, Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, BB 416, 650 West 168th St., New York, NY 10032. Phone: (212) 305-4193. Fax: (212) 305-2284. E-mail: asp7{at}columbia.edu.

Editor: E. I. Tuomanen

Infection and Immunity, January 2002, p. 127-133, Vol. 70, No. 1
0019-9567/01/$04.00+0     DOI: 10.1128/IAI.70.1.127-133.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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