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Infection and Immunity, December 1998, p. 5994-5998, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Internalization of Staphylococcus aureus by Endothelial Cells Induces Apoptosis

Barbara E. Menzies,1,2,* and Iordanka Kourteva1

Division of Infectious Diseases and Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232,1 and Department of Veterans Affairs Medical Center, Nashville, Tennessee 372122

Received 22 July 1998/Returned for modification 11 August 1998/Accepted 24 August 1998

The ability of Staphylococcus aureus to invade and survive within endothelial cells is believed to contribute to its propensity to cause persistent endovascular infection with endothelial destruction. In the present study, we show that following invasion of human umbilical vein endothelial cells, intracellular S. aureus organisms remain viable over a 72-h period and, as determined by transmission electron microscopic examination, that the bacteria exist within vacuoles and free within the cytoplasm. We also demonstrate that endothelial cell death following S. aureus invasion occurs at least in part by apoptosis as shown by DNA fragmentation and changes in nuclear morphology. Apoptotic changes were evident as early as 1 h after infection of endothelial cells. Internalization of S. aureus rather than adherence appears to be necessary, since use of the phagocytosis inhibitor cytochalasin D prevented apoptosis. UV-killed staphylococci, although retaining the capacity to be internalized, were not capable of inducing apoptosis, suggesting that apoptosis is dependent upon a factor associated with viable organisms. The studies demonstrate that viable intracellular S. aureus induces apoptosis of endothelial cells and that internalized staphylococci can exist free within the cytoplasm.

* Corresponding author. Mailing address: Division of Infectious Diseases, A-3310 Medical Center North, Vanderbilt University, Nashville, TN 37232-2605. Phone: (615) 327-4751, ext. 5495. Fax: (615) 343-6160. E-mail: menziebe{at}ctrvax.vanderbilt.edu.

Infection and Immunity, December 1998, p. 5994-5998, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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Copyright © 1998 by the American Society for Microbiology. All rights reserved.