Current Research Interests                                                                    Extreme Softball

Pathogenesis and Its Relationship to the Molecular Genetics of Invasive  Bacteria

Our research is driven by an interest in bacterial pathogenesis and its relationship with microbial physiology, structure, and genetics. Treponema pallidum (the causative agent of syphilis) and Borrelia burgdorferi (which causes Lyme disease) are spirochetes that cause chronic, multisystemic diseases.  Mycobacterium tuberculosis infects over 3 billion people worldwide and is estimated to cause over 1.5 million deaths per year.   These organisms are highly invasive and cause long-term systemic infections, and thus serve as excellent models for the study of host-pathogen interactions. Little is known about T. pallidum due to the inability to culture the organism continuously in vitro. We have thus concentrated our efforts on the global characterization of the T. pallidum genome as a means of determining the organism's genetic capabilities. In collaboration with Dr. George Weinstock and the Institute of Genomic Research in Rockville, Md., the complete sequence analysis of the 1.14 megabase chromosome of T. pallidum was completed in 1998. The genome sequence is being utilized to determine the nutritional requirements and to identify important antigens and virulence determinants of this enigmatic organism.  The sequence of the 2.84 megabase genome of Treponema denticola, an oral spirochete involved in periodontal disease, was published in April 2004.  We are currently applying ‘functional genomics’ to the elucidation of the spirochete's metabolism, structure, immunogenicity, and pathogenic mechanisms. In the case of B. burgdorferi, molecular genetic techniques such as gene inactivation and complementation, transposon mutagenesis, PCR, and reverse genomics are being utilized in combination with infectivity and gene complementation studies to identify DNA segments and proteins present in infectious strains but lacking in noninfectious variants. Thus far, we have identified and characterized the vls antigenic variation of B. burgdorferi, an elaborate mechanism similar to the Variable Major Protein system of relapsing fever borreliae. In addition, we have determined that the linear plasmids lp25 (and its encoded gene pncA) and lp28-1 are required for full virulence of B. burgdorferi during infection in mice.  Using signature-tagged mutagenesis and other molecular techniques, we are now taking a more global approach to identify additional genes encoding virulence determinants important in the pathogenesis of Lyme disease.  Our laboratory is also participating in the identification of important virulence factors and immunogens of M. tuberculosis through molecular genetic means.

Recent Publications

Brinkman, M. B., M. A. McGill, J. Petterson, A. Rogers, P. Matejkova, D. Smajs, G. M. Weinstock, S. J. Norris, and T. Palzkill. 2008. A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that binds human fibronectin. Infect. Immun. In press.
Strouhal, M., D. Smajs, P. Matejkova, E. Sodergren, A. G. Amin, J. K. Howell, S. J. Norris, and G. M. Weinstock. 2007. Genome differences between Treponema pallidum subsp. pallidum strain Nichols and T. paraluiscuniculi Strain Cuniculi A. Infect. Immun. 75:5859-5866. Abstract
Botkin, D. J., A. N. Abbott, P. E. Stewart, P. A. Rosa, H. Kawabata, H. Watanabe, and S. J. Norris. 2006. Identification of potential virulence determinants by Himar1 transposition of infectious Borrelia burgdorferi B31. Infect. Immun. 74:6690-9.  Abstract  
Norris, S. J. 2006. Antigenic variation with a twist - the Borrelia story. Mol. Microbiol. 60:1319-22. Abstract
Bykowski, T., K. Babb, K. von Lackum, S. P. Riley, S. J. Norris, and B. Stevenson.  2006.  Transcriptional regulation of the Borrelia burgdorferi antigenically variable VlsE surface protein.  J. Bacteriol. 188:4879-4889. Abstract
Jacobs, M. B., S. J. Norris, K. M. Phillippi-Falkenstein, and M. T. Philipp. 2006.  Infectivity via ticks of the highly transformable BBE02-, lp56- mutant of Borrelia burgdorferi, the Lyme disease spirochete.  Infect. Immun.  74:3678-3681.  Abstract
Norris, S. J.  2006.  The dynamic proteome of Lyme disease Borrelia.  (Review) Genome Biol. 7(3):209.  Abstract
Brinkman, M.B., McKevitt, M., McLoughlin, M., Perez, C., Howell, J., Weinstock, G.M., Norris, S.J., and Palzkill, T. (2006) Reactivity of antibodies from syphilis Patients to a protein array representing the Treponema pallidum proteome. J. Clin. Microbiol. 44: 888-891.  Abstract
McKevitt, M., M. B. Brinkman, M. McLoughlin, C. Perez, J. K. Howell, G. M. Weinstock, S. J. Norris, and T. Palzkill. 2005. Genome scale identification of Treponema pallidum antigens. Infect. Immun. 73:4445-50.  Abstract
Bertin, P. B., S. P. Lozzi, J. K. Howell, G. Restrepo-Cadavid, D. Neves, A. R. L. Teixeira, M. V. de Sousa, S. J. Norris, and J. M. Santana.  2005.  The thermophilic, homohexameric aminopeptidase of Borrelia burgdorferi (TAPBb) is a member of the M29 family of metallopeptidases.  Infect. Immun. 73:2253-2261.  Abstract
Copenhaver, R. H., E. Sepulveda, L. Armitige, A. Wanger, J. K. Actor, S. J. Norris, R. L. Hunter and C. Jagannath.  2004.  A mutant of Mycobacterium tuberculosis H37Rv that lacks the expression of antigen 85A is attenuated in mice but retains a vaccinogenic potential.  Infect. Immun.  72(12):7084-7095.  Abstract
Šmajs, D., M. McKevitt,  J. K. Howell, S. J. Norris, W.-W. Cai, T. Palzkill and G. M. Weinstock.  2005.  Transcriptome of Treponema pallidum: gene expression profile during experimental rabbit infection.  J Bacteriol 187:1866-74.  Abstract
Kawabata, H., S. J. Norris, and H. Watanabe. 2004. BBE02 Disruption mutants of Borrelia burgdorferi B31 have a highly transformable, infectious phenotype. Infect. Immun. 72:7147-54.  Abstract
Norris, S. J.  2004.  Chapter 70.  Spirochetes.  In W. Tasman and E. A. Jaeger (eds.), Duane’s Foundations of Clinical Ophthalmology.  Volume 2, p. 1-12.  Lippencott, Williams, and Wilkins, Philadelphia.
Copenhaver, R. H., E. Sepulveda, L. Y. Armitige, J. K. Actor, A. Wanger, S. J. Norris, R. L. Hunter, and C. Jagannath. 2004. A mutant of Mycobacterium tuberculosis H37Rv that lacks expression of Antigen 85A is attenuated in mice but retains vaccinogenic potential. Infect. Immun. 72:7084-7095.  Abstract
Lawrenz, M. B., R. M. Wooten, and S. J. Norris.  2004.  Effects of vlsE complementation on the infectivity of Borrelia burgdorferi lacking the linear plasmid lp28-1.  Infect. Immun. 72 (11):6577-6785.  Abstract
Norris, S. J.  2004.  Chapter 70.  Spirochetes.  In W. Tasman and E. A. Jaeger (eds.), Duane’s Foundations of Clinical Ophthalmology.  Volume 2, p. 1-12.  Lippencott, Williams, and Wilkins, Philadelphia.
Seshadri, R., G. S. A. Myers, H. Tettelin, J. A. Eisen, J. F. Heidelberg, R. J. Dodson, T. M. Davidsen, R. T. DeBoy, D. E. Fouts, D. H. Haft, J. Selengut, Q. Ren, L. M. Brinkac, R. Madupu, J. Kolonay, S. A. Durkin, S. C. Daugherty, J. Shetty, A. Shvartsbeyn, E. Gebregeorgis, K. Geer, G. Tsegaye, J. Malek, B. Ayodeji, S. Shatsman, M. P. McLeod, D. Šmajs, J. K. Howell, S. Pal, A. Amin, P. Vashisth, T. Z. McNeill, Q. Xiang, E. Sodergren, E. Baca, G. M. Weinstock, S. J. Norris, C. M. Fraser and I. T. Paulsen. 2004.  Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes.  Proc. Natl. Acad. Sci. U.S.A. 101:5646-5651.  Abstract
Šmajs, D., S. J. Norris, and G. M. Weinstock. 2004. Construction of Small Genome BAC Library for Functional and Genomic Applications. Methods Mol. Biol. 255:47-56.  Abstract
McKevitt, M., K. Patel, D. Šmajs, M. Marsh, M. McLoughlin, S. J. Norris, G. M. Weinstock, and T. Palzkill.  2003.  Systematic cloning of Treponema pallidum open reading frames for protein expression and antigen recovery.  Genome Res. 13:1665-1674. Abstract and full text article
Lawrenz, M. B., R. M. Wooten, J. F. Zachary, S. M. Drouin, J. J. Weis, R. A. Wetsel, and S. J. Norris. 2003. Effect of complement component C3 deficiency on experimental Lyme borreliosis in mice. Infect. Immun. 71:4432-4440. Abstract and full text article
 Iyer, R., O. Kalu, J. Purser, S. Norris, B. Stevenson, and I. Schwartz.  2003.  Linear and circular plasmid content in Borrelia burgdorferi clinical isolates.  Infect. Immun. 71(7):3699-3706. Abstract and full text article
 Purser, J. E., M. B. Lawrenz, M. J. Caimano, J. D. Radolf,  and S. J. Norris.  2003.  A plasmid-encoded nicotinamidase (PncA) is essential for infectivity of Borrelia burgdorferi in a mammalian host.  Molec. Microbiol. 48(3):753-764. Abstract and full text article
Wang, D., D. J. Botkin, and S. J. Norris.  2003.  Characterization of the vls antigenic variation loci of the Lyme disease spirochetes Borrelia garinii Ip90 and Borrelia afzelii ACAI.  Molec. Microbiol. 47:1407-1417. Abstract and full text article
Mueller-Ortiz, S. L. E. Sepulveda, M. R. Olsen, C. Jagannath, A. R. Wanger, and S. J. Norris.  2002.  Decreased infectivity despite unaltered C3 binding by a DhbhA mutant of Mycobacterium tuberculosis.  Infect. Immun. 70(12):6751-6760. Abstract and full text article
Lawrenz, M. B., H. Kawabata, J. E. Purser, and S. J. Norris. 2002. Decreased electroporation efficiency in Borrelia burgdorferi containing linear plasmids lp25 and lp56: implications in transformation of infectious Borrelia. Infect. Immun. 70:4798-4804.  Abstract and full text article
Eicken, C., V. Sharma, T. Klabunde, M. B. Lawrenz, J. M. Hardham, S. J. Norris, and J. C. Sacchettini. 2002. Crystal structure of the variable surface antigen VlsE of Borrelia burgdorferi. J. Biol. Chem. 277(24):21691-6.  Abstract and full text article
Šmajs, D., M. McKevitt, L. Wang, J. K. Howell, S. J. Norris, T. Palzkill, and G. M. Weinstock. 2002. BAC Library of T. pallidum DNA in E. coli. Genome Res 12:515-522.  Abstract and full text article
Mueller-Ortiz, S. L., A. R. Wanger, and S. J. Norris. 2001. Mycobacterial protein HbhA binds human complement component C3. Infect Immun 69:7501-7511. Abstract and full text article
Indest, K. J., J. K. Howell, M. B. Jacobs, D. Scholl-Meeker, S. J. Norris, and M. T. Philipp. 2001. Analysis of Borrelia burgdorferi vlsE gene expression and recombination in the tick vector. Infect Immun 69:7083-7090.  Abstract and full text article
Norris, S. J., D. L. Cox, and G. M. Weinstock. 2001. Biology of Treponema pallidum: Correlation of functional activities with genome sequence data. J. Molec. Microbiol. Biotechnol. 3:37-62. Abstract
Purser, J. E., and S. J. Norris. 2000. Correlation between plasmid content and infectivity in Borrelia burgdorferi. Proc. Natl. Acad. Sci. USA 97:13865-13870. Abstract
Weinstock, G. M., D. Smajs, J. Hardham, and S. J. Norris. 2000. From microbial genome sequence to applications. Res. Microbiol. 151:1-8. Abstract
Norris, S. J., and G. M. Weinstock. 2000. The genome sequence of Treponema pallidum, the syphilis spirochete: will clinicians benefit? Curr. Opinion Infect. Dis. 13:29-36. 
Iyer, R., J. M. Hardham, G. P. Wormser, I. Schwartz, and S. J. Norris. 2000. Conservation and heterogeneity of vlsE among human and tick isolates of Borrelia burgdorferi. Infect. Immun. 68:1714-1718. Abstract
Armitige, L. Y., A. R. Wanger, and S. J. Norris. 2000. Disruption of the genes encoding Antigen 85A and Antigen 85B of Mycobacterium tuberculosis; effects on growth in medium and in macrophage cultures. Infect. Immun 68(2):767-78. Abstract
Pennington, P. M., D. Cadavid, J. Bunikis, S. J. Norris, and A. G. Barbour. 1999. Extensive interplasmidic duplications change the virulence phenotype of the relapsing fever agent Borrelia turicatae. Molec. Microbiol. 34(5):1120-32. Abstract
Lawrenz, M. B., J. M. Hardham, R. T. Owens, J. Nowakowski, A. C. Steere, G. P. Wormser, and S. J. Norris. 1999. Human antibody responses to the VlsE antigenic variation protein of Borrelia burgdorferi. J. Clin. Microbiol. 37:3997-4004. Abstract
Posey J. E., J. M. Hardham, S. J. Norris, F. C. Gherardini. 1999. Characterization of a manganese-dependent regulatory protein, TroR, from Treponema pallidum. Proc Natl Acad Sci U S A 96:10887-10892. Abstract  
Fraser, C. M., S. J. Norris, G. M. Weinstock, O. White, G. G. Sutton, R. Dodson, M. Gwinn, E. K. Hickey, R. Clayton, K. A. Ketchum, E. Sodergren, J. M. Hardham, M. P. McLeod, S. Salzberg, J. Peterson, H. Khalak, D. Richardson, J. K. Howell, M. Chidambaram, T. Utterback, L. McDonald, P. Artiach, C. Bowman, M. D. Cotton, C. Fujii, S. Garland, B. Hatch, K. Horst, K. Roberts, L. Watthey, Janice W., H. O. Smith, and C. J. Craig Venter. 1998. Complete genome sequence of Treponema pallidum, the syphilis spirochete. Science 281:375-388. Abstract
Weinstock, G. M., J. M. Hardham, M. P. McLeod, E. J. Sodergren, and Steven J. Norris. 1998. The genome of Treponema pallidum: new light on the agent of syphilis. FEMS Microbiol. Rev. 22:323-32. Abstract
Zhang, J.-R. and S. J. Norris. 1998. Genetic variation of the Borrelia burgdorferi gene vlsE protein involves cassette-restricted, segmental gene conversion. Infect. Immun. 66: 3698-3704. Abstract
Zhang, J.-R. and S. J. Norris. 1998. Kinetics and in vivo induction of genetic variation of vlsE in Borrelia burgdorferi. Infect. Immun. 66: 3689-3697. Abstract
Pride, M. W., E. L. Brown, L. C. Stephens, J. J. Killion, S. J. Norris, and M. L. Kripke. 1998. Specific Th1 cell lines that confer protective immunity against experimental Borrelia burgdorferi infection in mice. J. Leukocyte Biol. 63:542-549. Abstract
Norris S. J., C. M. Fraser, and G. M. Weinstock. 1998. Illuminating the agent of syphilis: the Treponema pallidum genome project. Electrophoresis. 19:551-3. Abstract
Zhang, J.-R., J. M. Hardham, A. G. Barbour, and S. J. Norris. 1997. Antigenic variation in Lyme disease borreliae by promiscuous recombination of VMP-like sequence cassettes. Cell 89:275-285. Abstract

Links

Brief Curriculum Vitae 

Microbial Pathogenesis 2004 Course

Bioterrorism Defense and Preparedness 2003

Treponema Molecular Genetics Server