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Infection and Immunity, November 1998, p. 5238-5243, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Staphylococcus aureus Agr and Sar Global
Regulators Influence Internalization and Induction of
Apoptosis
Carla A.
Wesson,
Linda E.
Liou,
Kristine M.
Todd,
Gregory
A.
Bohach,
William R.
Trumble, and
Kenneth W.
Bayles*
Department of Microbiology, Molecular Biology
and Biochemistry, University of Idaho, Moscow, Idaho 83844-3052
Received 8 June 1998/Returned for modification 10 August
1998/Accepted 25 August 1998
Staphylococcus aureus was recently shown to be
internalized by and to induce apoptosis in a bovine mammary epithelial
cell line, suggesting that these processes could be involved in
staphylococcal pathogenesis or persistence. To examine the role of
virulence factor regulators during internalization, mutant
agr and sar strains of S. aureus
were analyzed for their abilities to enter and induce apoptosis in
epithelial cells. Like a previously characterized bovine mastitis
isolate, the standard laboratory strain, RN6390 (wild type), entered
the epithelial cells and subsequently induced apoptosis. In contrast,
the mutant strains RN6911 (agr), ALC136 (sar),
and ALC135 (agr sar) were internalized by the cultured cells at levels reproducibly greater than that for RN6390 but failed to
induce apoptosis. The internalization of S. aureus was affected by growth phase, suggesting a role for
agr-regulated surface proteins in this process.
Furthermore, the ability to induce apoptosis required metabolically
active intracellular bacteria. These data indicate that the ability of
S. aureus to enter mammalian cells and induce apoptosis is
dependent on factors regulated by Agr and Sar. Since transcriptional
control by these global regulators is mediated by quorum-sensing and
environmental factors, staphylococci may have the potential to induce
several alternative effects on cells from an intracellular environment.
A model for the function of the agr locus in the context of
internalization, intracellular persistence, and dissemination is
proposed.
*
Corresponding author. Mailing address: Department of
Microbiology, Molecular Biology and Biochemistry, College of
Agriculture, University of Idaho, Moscow, ID 83844-3052. Phone (208)
885-7164. Fax: (208) 885-6518. E-mail: kbayles{at}uidaho.edu.
Infection and Immunity, November 1998, p. 5238-5243, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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