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Infection and Immunity, June 2005, p. 3261-3270, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3261-3270.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Glucosyltransferases of Viridans Streptococci Are Modulins of Interleukin-6 Induction in Infective Endocarditis

Chia-Tung Shun,1 Shih-Yu Lu,2 Chiou-Yueh Yeh,2 Chung-Pin Chiang,3 Jean-San Chia,2,3* and Jen-Yang Chen2,4

Department of Forensic Medicine,1 Graduate Institute of Microbiology, College of Medicine, National Taiwan University,2 Department of Oral Diagnosis and Pathology, National Taiwan University Hospital,3 National Health Research Institute, Taipei, Taiwan, Republic of China4

Received 16 September 2004/ Returned for modification 8 December 2004/ Accepted 3 February 2005

The glucosyltransferases (GTFs) of viridans streptococci, common pathogens of infective endocarditis, are extracellular proteins that convert sucrose into exopolysaccharides and glucans. GTFs B, C, and D of Streptococcus mutans are modulins that induce, in vitro and in vivo, the production of cytokines, in particular interleukin-6 (IL-6), from monocytes. The roles of S. mutans GTFs in infectivity and inflammation in situ were tested in a rat experimental model of endocarditis. No significant differences in infectivity, in terms of 95% infective dose and densities of bacteria inside vegetations, were observed between laboratory strain GS-5 and two clinical isolates or isogenic mutant NHS1DD, defective in the expression of GTFs. In aortic valves and surrounding tissues, IL-6 was detected by Western blots and immunostaining 24 h after GS-5 infection, was maintained over 72 h, and was followed by production of tumor necrosis factor alpha but not IL-1ß. Animals infected with NHS1DD showed markedly lower levels of IL-6 (less than 5% of that of parental GS-5-infected rats), while tumor necrosis factor alpha was unaffected. In contrast, animals infected with NHR1DD, another isogenic mutant expressing only GtfB, showed a much smaller reduction (down to 56%). These results suggest that GTFs are specific modulins that act during acute inflammation, inducing IL-6 from endothelial cells surrounding the infected valves without affecting bacterial colonization in vegetations, and that IL-6 might persist in chronic inflammation in endocarditis.

* Corresponding author. Mailing address: No. 1, Jen Ai Road, 1st Section, Room 713, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. Phone: 886-2-23123456, ext. 8222. Fax: 886-2-23926238. E-mail: chiajs{at}ha.mc.ntu.edu.tw.

Editor: V. J. DiRita

Infection and Immunity, June 2005, p. 3261-3270, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3261-3270.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Nemoto, H., Nakano, K., Nomura, R., Ooshima, T. (2008). Molecular characterization of Streptococcus mutans strains isolated from the heart valve of an infective endocarditis patient. J Med Microbiol 57: 891-895 [Abstract] [Full Text]  
  • Nomura, R., Nakano, K., Nemoto, H., Fujita, K., Inagaki, S., Takahashi, T., Taniguchi, K., Takeda, M., Yoshioka, H., Amano, A., Ooshima, T. (2006). Isolation and characterization of Streptococcus mutans in heart valve and dental plaque specimens from a patient with infective endocarditis.. J Med Microbiol 55: 1135-1140 [Abstract] [Full Text]  
  • Yeh, C.-Y., Chen, J.-Y., Chia, J.-S. (2006). Glucosyltransferases of Viridans Group Streptococci Modulate Interleukin-6 and Adhesion Molecule Expression in Endothelial Cells and Augment Monocytic Cell Adherence. Infect. Immun. 74: 1273-1283 [Abstract] [Full Text]  


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