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Infection and Immunity, May 2003, p. 2716-2723, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2716-2723.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Strain-Specific Association of Cytotoxic Activity and Virulence of Clinical Staphylococcus aureus Isolates

Oleg Krut, Olaf Utermöhlen, Xenia Schlossherr, and Martin Krönke*

Institute for Medical Microbiology, Immunology, and Hygiene, Medical Center University of Cologne, 50935 Cologne, Germany

Received 4 September 2002/ Returned for modification 22 October 2002/ Accepted 21 January 2003

Staphylococcus aureus has been shown to invade and induce the death of various cell types. Here we investigate whether the cytotoxicity of intracellular S. aureus is a general feature or rather characteristic of individual S. aureus strains. The majority of 23 randomly collected clinical S. aureus isolates were killed inside keratinocytes and fibroblasts, indicating that the uptake of S. aureus represents an important mechanism of cell-autonomous host defense. However, seven independent S. aureus isolates survived intracellularly and induced significant cytotoxicity for their host cells. Subcloning analysis revealed that the ability or inability to kill host cells is a stable, apparently genetically determined trait of a given S. aureus isolate. We show that noncytotoxic strains but not cytotoxic strains colocalize with the lysosomal marker LAMP-1, suggesting that only cytotoxic strains escape degradation by the endolysosomal pathway. In a mouse septicemic model, cytotoxic S. aureus isolates produce significantly greater lethality (96%) compared to noncytotoxic strains (41%), which corresponds to 23-, 63-, and 30,000-fold increases of bacterial loads in the liver, spleen, and kidney, respectively. Finally, cytotoxic S. aureus strains produce clinically apparent arthritis in mice at a greater frequency than compared to noncytotoxic S. aureus strains. The results of our study unravel a previously unrecognized dichotomy of cytotoxic and noncytotoxic S. aureus isolates, which may play an important role in the dissemination of, and mortality induced by, S. aureus infection.

* Corresponding author. Mailing address: Institute for Medical Microbiology, Immunology, and Hygiene, Medical Center, University of Cologne, Goldenfelsstr. 19-21, 50935 Cologne, Germany. Phone: 49-221-4783060. Fax: 49-221-4783067. E-mail: Martin.Kroenke{at}medizin.uni-koeln.de.

Editor: A. D. O'Brien

Infection and Immunity, May 2003, p. 2716-2723, Vol. 71, No. 5
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.5.2716-2723.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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