Michael Caparon Associate Professor Phone, office: (314)-362-1485 Phone, lab: (314)-362-7650 FAX: (314)-362-1232 email: caparon@borcim.wustl.edu Online: http://www.caparonlab.wustl.edu 10250 McDonnell Pediatric Research Building Box 8230 Department of Molecular Microbiology Washington University School of Medicine 660 South Euclid Avenue St. Louis, MO 63110-1093.

Research Interests | CV | Publications | Technology for licensing

Research Interests

Specific projects include the analysis of two surface proteins of S. pyogenes that direct its initial interaction with host cells. One protein, known as the M protein, functions to allow the bacterium to adhere to keratinocytes during infection of the skin; while protein F, fibronectin-binding protein, mediates the attachment of S. pyogenes to epidermal Langerhans cells. The capacity to control the expression of adhesins for specific cell types has allowed an examination of the effect of adherence to a host cell on the pathogen-host interaction. These studies have shown that these adhesive interactions coordinate the targeting of other secreted streptococcal molecules which then act in combination to influence the signaling pathways that these host cells use to orchestrate the inflammatory response.

Expression of the adhesins and the other secreted molecules is tightly regulated in response to several environment cues, including O2. Genes involved in regulation have been identified (mga, rofA, gasK1K2R, ropB, tig) and their role in regulation is under analysis using state of the art tools we are developing for S. pyogenes, including novel methods of transposon mutagenesis which can specifically identify gene products secreted from gram positive bacteria.

CV

Publications

1. Caparon, M.G. and Scott, J.R. (1987). Identification of a gene that regulates expression of M.protein, the major virulence determinant of group A streptococci. Proc. Natl. Acad. Sci. USA 84:8677-8681.
2. Caparon, M.G. and Johnson, W. (1988). Macrophage toxicity and complement sensitivity of virulent and avirulent strains of Legionella pneumophila. Rev. Infect. Dis. 10:S377-S381.
3. Scott, J.R., Kirchman, P.A., Caparon, M.G. (1988). An intermediate in transposition of the conjugative transposon Tn 916. Proc. Natl. Acad. USA Sci 85: 4809-4813.
4. Norgren, M., Caparon, M.G. and Scott, J.R. (1989). A method for allelic replacement using the conjugative transposon Tn916: deletion of the emm 6.1 allele in Streptococcus pyogenes. Infect. Immun. 57: 3856-3862.
5. Caparon, M.G. and Scott, J.R. (1989). Excision and Insertion of the conjugative transposon Tn916 involves a novel recombination mechanism. Cell. 59: 1027-1034.
6. Caparon, M.G., D.S. Stevens, A. Olsen, and J.R. Scott. (1991). Role of M protein in adherence of group A streptococci. Infect. Immun. 59:1811-1817.
7. Perez-Casal, J., Caparon, M. G. and Scott, J. R.. (1991). Mry, a trans -acting positive regulator of the M protein gene of Streptococcus pyogenes with similarity to the receptor proteins of two-component regulatory systems. J. Bacteriol. 173:2617-2624.
8. Hanski, E. and Caparon, M. G. (1992). Protein F, a fibronectin-binding protein, is an adhesin of the group A streptococcus. Proc. Natl. Acad. Sci. USA. 89:6172-6176.
9. Caparon, M. G., R. T. Geist, J. Perez-Casal and J. R. Scott. 1992. Environmental reglation of virulence in group A streptococci: Transcription of the gene encoding the M protein is stimulated by carbon dioxide. J. Bacteriol. 174:5693-5701.
10. Perez-Casal, J., M. G. Caparon, and J. R. Scott. 1992. Introduction of the emm 6 gene into an emm-deletion strain of Streptococcus pyogenes restores its ability to resist phagocytosis. Res. in Microbiol. 143:549-558.
11. Hanski, E., P. Horwitz, and M. G. Caparon. 1992. Introduction of protein F, the fibronectin-binding protein of Streptococcus pyogenes JRS4, into heterologous streptococcal and enterococcal strains promotes their adherence to respiratory epithelial cells. Infect. Immun. 60:5119-5125.
12. Okada, N., R. T. Geist, and M. G. Caparon. 1993. Positive transcriptional control of mry regulates virulence in the group A streptococcus. Mol. Microbiol. 7:893-903.
13. VanHeyningen, T., G. Fogg, D. Yates, E. Hanski and M. G. Caparon. 1993. Adherence and fibronectin-binding are environmentally regulated in group A streptococci. Mol. Microbiol. 9:1213-1221.
14. Geist, R. T., N. Okada, and M. G. Caparon. 1993. Analysis of Streptococcus pyogenes promoters using Novel Tn916 -based shuttle vectors for the construction of transcriptional fusions to CAT. J. Bacteriol. 175:7561-7570.
15. Sela, S., A. Aviv, A. Tovi, I. Burstein, M. G. Caparon, and E. Hanski. 1994. Protein F-An adhesin of Streptococcus pyogenes binds fibronectin via two distinct domains at two different binding sites. Mol. Microbiol. 10:1049-1055.
16. Fogg, G., C. Gibson, and M. G. Caparon. 1994. The identification of rofA , a positive-acting regulatory component of prtF expression: Use of a mgd-based shuttle mutagenesis strategy in Streptococcus pyogenes. Mol. Microbiol. 11:671-684.
17. Okada, N., A. P. Pentland, P. Falk and M. G. Caparon. 1994. M protein and protein F act as Important Determinants of Cell-Specific Tropism of Streptococcus pyogenes in Skin Tissue. J. Clin. Invest. 94:965-977.
18. Perez-Casal, J. N. Okada, M. Caparon and J. R. Scott. 1995. Role of the conserved C repeat region of the M protein of Streptococcus pyogenes. Mol. Microbiol. 15:907-916.
19. Okada, N. K. Liszewski, J. P. Atkinson and M. Caparon. 1995. Membrane co-factor protein (MCP or CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. Proc. Natl. Acad. Sci. USA. 92:2489-2493
20. Natanson, S., S. Sela, A. Moses, J. M. Musser, M. G. Caparon and E. Hanski. 1995. Distribution of fibronectin-binding proteins among group A streptococci of different M types. J. Infect. Dis. 171:871-878.30.
21. Lee, Ju-Y., and M. Caparon. 1995. An oxygen induced, but protein F-independent, fibronectin binding pathway in Streptococcus pyogenes. Infect. Immun. In press.
22. Kihlberg, B.-M., J. Cooney, M. G. Caparon, A. OlsŽn, and L. Bjšrck. 1995. Biological proterties of Streptococcus pyogenes type M1 mutants generated by Tn916 mutation in mga. Microbial Pathogenesis. In press.
23. Ozeri, V., A. Tovi, I. Burstein, S. Natanson-Yaron, M. G. Caparon, K. M. Yamada, S. K. Akiyama, I. Vlodavsky and E. Hanski. 1995. A novel two-domain mechanism for streptococcal adhesion to fibronectin. EMBO J. 15:989-998. Lee, Ju-Y., and M. Caparon. 1996. An oxygen-induced but protein F-independent fibronectin binding pathway in Streptococcus pyogenes. Infect. Immun. 64:413-421.

24. Jaffe, J., S. Natanson-Yaron, M. G. Caparon and E. Hanski. 1996. Protein F2, a novel fibronectin ginding protein from Streptococcus pyogenes posses two binding domains. Mol. Microbiol. 21:373-384.

25. Gibson, C. M., and M. G. Caparon. 1996. Insertional inactivation of Streptococcus pyogenes sod suggests prtF is regulated in response to a superoxide signal. J. Bacteriol. 178:4688-4695.

26. Wang, B., N. Ruiz, A. Pentland, and M. Caparon. 1997. Keratinocyte proinflammaroy responses to adherent and non-adherent group A streptococci. Infect. Immun. 65:2119-2126.

27. Fogg, G. C., and M. G. Caparon. 1997. Constitutive expression of fibronectin-binding in Streptococcus pyogenes as a result of anaerobic activation of rofA. J. Bacteriol. 179:6172-6180.

28. Okada, N., M. Watarai, V. Ozeri, E. Hanski, M. Caparon and C. Sasakawa. A Matrix form of fibronectin mediates enhanced binding of Streptocococcus pyogenes to host tissue. J. Biol. Chem. 272:26987-26984.

29. Ruiz, N., B. Wang, A. Pentland, and M. Caparon. 1997. Streptolysin O and adherence synergistically modulate proinflammatory responses of keratinocytes to group A streptococci. Mol. Microbiol. 27:337-346.

30. Lyon, W., C. Gibson, and M. Caparon. 1998. A role for Trigger Factor and an Rgg-like regulator in the transcription, secretion and processing of the cysteine proteinase of Streptococcus pyogenes. EMBO J. 21:6263-6275.

31. Gibson, C. M., T. C. Mallett, A. Claiborne, and M. G. Caparon. 1999. The contribution of NADH oxidase to the aerobic metabolism of Streptococcus pyogenes. J. Bacteriol. 182: 448-455.

32. Granok, A., D. Parsonage, R. P. Ross, and M. G. Caparon. 1999. The RofA binding site of Streptococcus pyogenes is utilized by multiple transcriptional pathways. J. Bacteriol. 182:1529-1540.

1. Caparon, M.G. and Scott, J.R. 1991. Genetic analysis of the Pathogenic Streptococci. Methods in Enzymology. 204:556-586.
2. Caparon, M. G. and J. R. Scott, J. R. 1993. The Streptococci. " Bacillus subtilis and other Gram-Positive Bacteria." J. A. Hoch, R. Losick, and A.L. Sonenshine, Eds. ASM Press.
3. OlsŽn, A., E. Hanski, S. Normark and M. G. Caparon. 1993. Molecular Analysis of bacterial fibronectin-binding. J. Microbiol. Meth. 18:213-226.
4. Hultgren, S. J., S. Abraham, M. G. Caparon, J. St. Geme, III., P. Falk, and S. Normark. 1993. Pilus and nonpilus bacterial adhesins: Assembly and function in cell recognition. Cell. 73:887-901.
5. Gibson, C., G. Fogg, N. Okada, R. T. Geist, E. Hanski and M. G. Caparon. 1994. Regulation of Host Cell Recognition in Streptococcus pyogenes. Dev. Microbiol. Stand. 85:137-144.
6. Hanski, E., G. Fogg, A. Tovi, N. Okada, I. Burstein, and M. G. Caparon. 1994. Molecular analysis of Streptococcus pyogenes adherence. Meth. Enzymol. 253:269-308.
7. Falk, P., T. BorŽn, D. Haslam and M. G. Caparon. 1994. Bacterial adhesion and colonization assays. Meth. Cell Biology. 45:161-187.

Technology for Licensing

• pCIV: A series of vectors based on the conjugative transposon Tn916 that can be used for analysis of gene expression in gram positive bacteria.
• m gamma delta.200: A mini-gamma delta-based transposon for shuttle mutagenesis of the genomes of gram positive bacteria.