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Infection and Immunity, November 2009, p. 4966-4975, Vol. 77, No. 11
0019-9567/09/$08.00+0 doi:10.1128/IAI.00760-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Comprehensive Evaluation of Streptococcus sanguinis Cell Wall-Anchored Proteins in Early Infective Endocarditis
,
Lauren Senty Turner,1,2
Taisei Kanamoto,1,
Takeshi Unoki,3,
Cindy L. Munro,3
Hui Wu,4 and
Todd Kitten1,2,5*
Philips Institute of Oral and Craniofacial Molecular Biology,1 Department of Microbiology and Immunology,2 Adult Health Nursing,3 Center for the Study of Biological Complexity, Virginia Commonwealth University, Richmond, Virginia,5 Departments of Pediatric Dentistry and Microbiology, Schools of Dentistry and Medicine, University of Alabama at Birmingham, Birmingham, Alabama4
Received 6 July 2009/ Returned for modification 30 July 2009/ Accepted 15 August 2009
Streptococcus sanguinis is a member of the viridans group of streptococci and a leading cause of the life-threatening endovascular disease infective endocarditis. Initial contact with the cardiac infection site is likely mediated by S. sanguinis surface proteins. In an attempt to identify the proteins required for this crucial step in pathogenesis, we searched for surface-exposed, cell wall-anchored proteins encoded by S. sanguinis and then used a targeted signature-tagged mutagenesis (STM) approach to evaluate their contributions to virulence. Thirty-three predicted cell wall-anchored proteins were identified—a number much larger than those found in related species. The requirement of each cell wall-anchored protein for infective endocarditis was assessed in the rabbit model. It was found that no single cell wall-anchored protein was essential for the development of early infective endocarditis. STM screening was also employed for the evaluation of three predicted sortase transpeptidase enzymes, which mediate the cell surface presentation of cell wall-anchored proteins. The sortase A mutant exhibited a modest (
2-fold) reduction in competitiveness, while the other two sortase mutants were indistinguishable from the parental strain. The combined results suggest that while cell wall-anchored proteins may play a role in S. sanguinis infective endocarditis, strategies designed to interfere with individual cell wall-anchored proteins or sortases would not be effective for disease prevention.
* Corresponding author. Mailing address: The Philips Institute of Oral and Craniofacial Molecular Biology, Virginia Commonwealth University, 521 North 11th Street, P.O. Box 980566, Richmond, VA 23298-0566. Phone: (804) 628-7010. Fax: (804) 828-0150. E-mail: tkitten{at}vcu.edu
Published ahead of print on 24 August 2009.
Supplemental material for this article may be found at http://iai.asm.org/.
Present address: Department of Microbiology, St. Marianna University School of Medicine, 2-16-1 Sugao Miyamae-ku, Kawasaki 216-8511, Japan.
Present address: St. Luke's College of Nursing, 10-1, Akashi-cho, Chuo-ku, Tokyo 104-0044, Japan.
Infection and Immunity, November 2009, p. 4966-4975, Vol. 77, No. 11
0019-9567/09/$08.00+0 doi:10.1128/IAI.00760-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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