Richard T. Marconi, Ph.D.
Professor

Phone: (804) 828-3779
Dept. Fax: (804) 828-9946
e-mail: rmarconi@vcu.edu

Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
P.O. Box 980678
1112 E. Clay St., 101 McGuire Hall
Richmond, VA 23298-0678

Lab Web Page

Professional Experience

• B.S., 1983, William Paterson College of New Jersey
• Ph.D., 1988, University of Montana
• Postdoctoral: 1989-1990, Roche Institute of Molecular Biology, Nutley, New Jersey;
• 1990-1994, NIAID, National Institutes of Health 
• Assistant Professor: 1994-1999, Virginia Commonwealth University
• Associate Professor: 1999-Present, Virginia Commonwealth University

Research Interests:

Pathogenic bacterial species of the genus Borrelia are the causative agents of several important diseases including Lyme disease, relapsing fever, epizootic bovine abortion, and avian and bovine borreliosis. Of these Lyme disease poses the greatest public health threat to humans and is now the most common tick-borne disease in North America and Europe. Its incidence has steadily increased and its endemic regions are expanding. These pathogens are transmitted to humans through the bite of infected Ixodes ricinus ticks. The resulting infection is a multi-system disorder with highly variable clinical manifestations and debilitating consequences. In the absence of treatment the infection is chronic indicating that these pathogens are able to evade the host immune response. The Borrelia genome is unique from that of all other bacteria. It is comprised of a linear chromosome and an extensive array of linear and circular plasmids. The Lyme disease spirochetes carry ~ 21 different plasmids which encode key virulence factors. Studies in my lab focus on the role of these plasmid encoded virulence factors in the molecular pathogenesis of Lyme disease and on the development of Lyme disease vaccines and diagnostic assays.

The three mains areas of research in my lab, funded through the National Institutes of Health, are:

1) Identification and characterization of Immune evasion mechanisms of the Lyme disease spirochetes.

We have recently identified and characterized novel mechanisms of evasion of both the antibody mediated and innate immune responses. Evasion of the antibody response occurs through antigenic variation of Borrelia surface proteins. Rapid mutation, recombination and alteration of the genes encoding the dominants surface antigens of these bacteria allow them to stay one step ahead of the antibody response and persist in their hosts. Evasion of the innate immune response is accomplished in part through the binding of the serum, complement regulatory protein, factor H. Binding of this protein to the bacterial surface decreases the efficiency of bacterial killing by the alternate complement cascade. We have also demonstrated that some dominant surface antigens are differentially and temporally expressed during infection suggesting that specific proteins are required during different stages of infection. Future analyses, employing knock out mutagenesis, will assess the role of these proteins in the mammalian host during the course of infection and identify the molecular interactions that occur between these proteins and their associated ligands.

2) Cell signaling. protein phosphorylation and environmental adaptation: the role of the Bdr protein family. The plasmid carried, bdr (Borrelia direct repeat) gene family, encodes proteins that may be involved in cell signaling and environmental adaptation. The bdr gene family is a complex gene family consisting of 18 members in B. burgdorferi B31MI. We have demonstrated that this gene family is carried by all pathogenic Borrelia species suggesting an important genus wide functional role. The maintenance of such a large gene family is energetically expensive and suggests that individual members of the family may carry out different functional roles. We have recently demonstrated that the bdr genes are differentially expressed and that there expression is regulated by environmental conditions. The presence of serine-threonine phosphorylation motifs within these proteins may indicate that they sense and transduce environmental signals through phosphorylation and dephosphorylation. In light of the radically different environments encountered by the Lyme disease spirochetes as they cycle between mammals and ticks (and microhabitats within these hosts), the ability of these bacteria to rapidly adapt to changing environmental parameters is critical to their survival. Studies are ongoing to specifically determine the role of these proteins in the host-pathogen interaction.

Research in our laboratory is funded by three National Institutes of Health grants. Our laboratory features an interactive team of researchers utilizing state of the art facilities that include (multiple real time PCR systems, standard platform PCR, immunofluoresence and darkfield microscopy, pulsed field gel electrophoresis systems, proteomics associated equipment and additional cutting edge tools for conducting molecular biology and molecular immunology based research. The lab also maintains sophisticated computer systems that allow for advanced data analysis.

Selected Publications:

Marconi, R. T., and Hill, W. E.: Evidence for a tRNA/rRNA interaction site within the peptidyltransferase center of the E. coli ribosome. Biochem . 28: 893-899, 1989.

Marconi, R. T., and Hill, W. E.: Identification of sequences in domain V of Escherichia coli 23S rRNA in the 50S subunit accessible for hybridization with oligonucleotides. Nucleic Acids Res . 16: 1603-1615, 1988.

Marconi, R. T., Lodmell, J. S., and Hill, W. E.: Ident. of a rRNA/chloramphenicol interaction site in the peptidyltransferase center of the 50S subunit of the E. coli ribosome. J. Biol. Chem . 265: 7894-7899, 1990.

Hill, W. E., Gluick, T., Marconi, R. T., Merryman, C., Tapprich, W., Tassanakajohn, A., and Weller, J. W.: Probing ribosome structure and function using short complementary DNA oligomers. In The Ribosome: Structure, Function and Evolution . Hill, W., Dahlberg, A., Garrett, R., Moore, P., Schlessinger, D., and Warner, J. (eds.), ASM Press, Washington , D.C. , pp. 253-261, 1990.

Marconi, R., Wigboldus, J., Weissbach, H., and Brot, N.: Transcriptional start and metR binding sites on the Escherichia coli metH gene. Biochem. Biophys. Res. Comm . 175: 1057-1063, 1991.

Marconi, R. T., and Garon, C. F.: Phylogenetic analysis of the genus Borrelia : a comparison of North American and European isolates of Borrelia burgdorferi . J. Bacteriol . 174: 241-244, 1992.

Marconi, R. T., and Garon, C. F.: Identification of a third genomic group of Borrelia burgdorferi through signature nucleotide analysis and 16S rRNA sequence determination. J. Gen. Micro . 138: 533-536, 1992.

Marconi, R. T., Lubke, L., Hauglum, W., and Garon, C. F.: Species-specific identification of and distinction between B. burgdorferi genomic groups by using 16S rRNA-directed oligo probes. J. Clin. Microbiol . 30: 628-632, 1992.

Marconi, R. T., and Garon, C. F.: Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. J. Clin. Microbiol . 30: 2830-2834, 1992.

Marconi, R. T., Samuels, D. S., and Garon, C. F.: Transcriptional analyses and mapping of the ospC gene in Lyme disease spirochetes. J. Bacteriol . 175: 926-932, 1993.

Marconi, R. T., Konkel, M. E., and Garon, C. F.: Variability of the osp gene products found among the species of Lyme disease spirochetes. Infect. Immun . 61:2611-2617. 1993.

Marconi, R. T., Samuels, D. S., Schwan, T. G., and Garon, C. F.: Identification of a protein in several species of Borrelia related to OspC of the Lyme spirochetes. J. Clin. Microbiol . 31:2577-2583. 1993.

Samuels, D. S., Marconi, R. T., and Garon, C. F.: Variation in the size of the osp A-containing linear plasmid and the linear chromosome among the three Borrelia species associated with Lyme disease. J. Gen. Microbiol . 139:2445-2449. 1993.

Samuels, D. S., Marconi, R.T., Huang, W. M. and Garon, C.F.: Mutations in gyrB from variants of Borrelia burgdorferi resistant to coumermycin A 1 . J. Bacteriol. 136:3072-3075. 1994.

Konkel, M. E., Marconi, R. T., Mead, D. J., and Cieplak, W.: Cloning, sequencing, and heterologous expression of a gene encoding HU from Campylobacter jejuni. Gene. 146:83-86. 1994.

Marconi, R. T., Samuels, D. S., and Garon, C. F.: Analysis of the distribution and molecular heterogeneity of the osp D gene among the Lyme disease spirochetes: Evidence for lateral gene exchange. J. Bacteriol. 176:4752-4582. 1994.

Feir, D., Santanello, C. R., Li, B.-W., Xie, C.-S., Masters, E., Marconi, R., and Weil, G.: Evidence supporting the presence of Borrelia burgdorferi in Missouri . J. Trop. Med. Hyg. 51:475-482. 1994.

Konkel, M. E., Marconi, R. T., Mead, D. J., and Cieplak, W.: Identification of an intervening sequence within the 23S rRNA genes of Campylobacter jejuni . Mol. Microbiol. 14:235-241. 1994

Marconi, R. T., Liveris, D, and Schwartz, I. : Identification of novel insertion elements, RFLP patterns, and discontinuous 23S rRNA in Lyme disease spirochetes:Phylogenetic analyses of rRNA genes and their intergenic spacers in Borrelia japonica sp. nov. and genomic group 21038 ( Borrelia andersonii sp. nov.) isolates. J. Clin. Microbiol. 33:2427-2434. 1995.

Marconi, R. T., Casjens, S., Munderloh, U.G., and Samuels, D. S.: Analysis of atypical linear plasmids in Borrelia burgdorferi sensu lato isolates: Implications concerning the potential mechanism of linear plasmid replication. J Bacteriol 178:3357-3361. 1996

Marconi. R.T., Sung, S. Y., Carlyon, J., and C. Norton-Hughes: Molecular and evolutionary analyses of a variable series of genes in Borrelia burgdorferi that are related to ospE and ospF , comprise a gene family, and that share a common upstream homology box. J. Bacteriol. 178:5615-5626. 1996.

Cloud, J. L., Marconi, R. T., Garon, C. F., Tilly, K., and D. S. Samuels.: Cloning and expression of the Borrelia burgdorferi lon gene. Gene 194:137-141. 1997.

Carlyon, J., LaVoie, C., Sung, S. Y., and R. T. Marconi.:Analysis of the organization of multicopy, linear and circular plasmid carried ORFs in Borrelia burgdorferi sensu lato isolates. Infect. Immun. 66:1149-1158. 1998.

Sung, S. Y., LaVoie, C., Carlyon, J., and R. T. Marconi.: Genetic divergence and evolutionary instability in ospE related members of the UHB gene family in Borrelia burgdorferi sensu lato complex isolates. Infect. Immun. 180:4974-4981. 1998.

Carlyon, J. A., and R. T. Marconi: Cloning and molecular characterization of a multi-copy, linear plasmid carried, repeat motif containing gene from Borrelia turicatae , a causative agent of Relapsing fever. J. Bacteriol. 66:4656-4668. 1998.

Carlyon, J.A., Roberts, D. M. and R. T. Marconi: Evolutionary and molecular analyses of the Borrelia bdr super gene family: Delineation of distinct sub-families and demonstration of the genus wide conservation of putative functional domains, structural properties and repeat motifs. Microbial Pathogenesis. 28:89-105.

Marconi, R. T. , Hohenberger, S., Jauris-Heipke, S., Schulte-Spechtel, U., LaVoie, C. P. , Rößler, D., and Wilske, B.: Genetic analysis of B. garinii OspA - serotype 4 strains associated with neuroborreliosis: evidence for extensive genetic homogeneity. J Clin Microbiol 37:3965-3970. 1999.

Sung, S. Y., McDowell, J., Carlyon, J.A.and R. T. Marconi: Mutation and recombination in the UHB flanked ospE related genes of the Lyme disease spirochetes results in the development of new antigenic variants during infection. Infection and Immunity 68:1319-1327. 2000.

Carlyon, J.A., Roberts, D.M., and R. T. Marconi: Molecular and immunological analyses of the Borrelia. turicatae Bdr protein family. Infect Immun . 68:2369-2373. 2000.

Roberts, D.M.,Theisen, M., Carlyon, J.A. and R.T. Marconi. The bdr gene families of the Lyme disease and relapsing fever spirochetes: possible influence on biology, pathogenesis and evolution. Emerg Infectious Dis . 6:110-122. 2000.

Roberts, D.M.,Theisen, M. and R.T. Marconi. Members of the Bdr protein family exhibit variable cellular localization in the Lyme disease and relapsing fever Borrelia . J. Bacteriol. 182:4222-4226. 2000

McDowell, J.V., Sung, S.-Y, and R.T. Marconi Analysis of the mechanisms associated with the loss of infectivity of clonal populations of Borrelia burgdorferi B31MI. Infect. Immun. 69:3670-3677. 2001.

Sung, S.-Y, McDowell, J.V. and R.T. Marconi. Demonstration of the role of post gene-conversion mutational events in generating vls variation in the Lyme disease spirochetes and evidence for constraints on the accumulation of vlsE mutations. J. Bacteriol . 183:5855-5861. 2001.

McDowell, J.V., Sung, S.-Y, Price, G. and R.T.Marconi. Demonstration of the genetic stability and temporal expression of select members of the Lyme disease spirochete OspF protein family during infection in mice. Infect. Immun . 69:4831-4838. 2001.

McDowell, J.V., Sung, S.-Y, Hu. L. T. and R.T. Marconi. Evidence that the variable regions of the central domain of VlsE are antigenic during infection with the Lyme disease spirochetes. Infect. Immun. 70:4196-4203. 2002

Roberts, D.M., Caimano. M., Radolf, J.R., Nelson, D, and R.T. Marconi. Environmental and differential expression of the Bdr Protein family of the Lyme disease spirochetes. Infect. Immun . 70:7033-41. 2002.

Metts, M.S.,McDowell, J.V., Theisen, M., Hansen, P.R. and R. T. Marconi. Analysis of the OspE determinants involved in the binding of factor H and OspE targeting antibodies elicited during Borrelia burgdorferi infection in mice. Infect. Immun. 71:3587-96. 2003.

McDowell, J.V., Tran, E., Hamilton , D., Metts, M.S., Wolfgang, J. and R. T. Marconi. Comprehensive analysis of the factor H binding capabilities of Borrelia species associated with Lyme disease: Demonstration of differential binding and delineation of distinct classes of factor H binding proteins. Infect. Immun. 71:3597-602. 2003.

McDowell, J.V., Tran, E., Hamilton , D., Wolfgang, J., Miller, K., and R.T. Marconi. Analysis of the ability of spirochete species associated with relapsing fever, avian borreliosis, and epizootic bovine abortion to bind factor H and cleave C3b. J. Clin. Microbiol. 41:3905-3910. 2003.

Miller, K., McDowell, J.V., Atkins, L., and R.T. Marconi. Identification and characterization of a linear plasmid encoded factor H binding protein (FhbA) of the Relapsing Fever Spirochete, Borrelia hermsii . J . Bacteriol .186:2612-2618.

McDowell, J.V., Wolfgang, J., Senty, L., Sundy, C. M. Noto, M. J. and R. T. Marconi. Demonstration of the involvement of OspE coiled-coil structural domains and higher order structural elements in the binding of infection induced antibody and the complement regulatory protein, factor H. J. Immunology. 173:7471-7480. 2004

Zhang, H-M., Raji, A., Theisen, M., Hansen, P. R. and R. T. Marconi. bdrF2 of the Lyme disease spirochetes is co-expressed with a series of cytoplasmic proteins and produced specifically during early infection.  J. Bacteriol. 187:175-184. 2005.

McDowell, J.V., Harlin, M E., Rogers, E., and R.T. Marconi. Putative coiled-coil structural elements of the BBA68 protein of the Lyme Disease Spirochetes are required for formation of its factor H binding site. J Bacteriol 187:1317-1323. 2005.

Earnhart, C. G., Dumler, J.S., and R.T. Marconi. Demonstration of OspC type diversity in invasive human Lyme disease isolates and identification of previously uncharacterized epitopes that define the specificity of the OspC antibody response. Infect. Immun. 73:7869-7877. 2005  

Zhang, H. and R. T. Marconi. Demonstration of co-transcription of a 30 gene operon from a 32 kb circular plasmid of Borrelia burgdorferi that is induced by the DNA alkylating agent, MNNG:  Additional evidence for the existence of bacteriophage. J. Bacteriol. 187:7895-7995. 2005. 

McDowell, J.V.,  Lankford, J., Stamm, L., Sadlon, T., Gordon, D.L.  and R. T. Marconi Demonstration of factor H Binding to the FhbB protein of Treponema denticola, a Pathogen Associated with Periodontal Disease in humans. Infect. Immun. 73:7126-7132. 2005 

McDowell, J.V., Hovis, K.M., and R.T. Marconi; Evidence that the factor H binding BBA68 (BbCRASP-1) protein of the Lyme disease spirochetes does not contribute to factor H mediated immune evasion in humans and other animals. Infect. Immun. 74:3030-4. 2006. 

Hovis, K M, Tran, E., Sundy, CM, Buckles, E, McDowell, J V and R. T. Marconi.  Selective binding of Borrelia burgdorferi OspE Paralogs to Factor H and Serum Proteins from Diverse Animals: possible expansion of the role of OspE in Lyme disease pathogenesis. Infect. Immun. 74:1967-72. 2006. 

Hovis, K.M, Sadlon, T., Raval, G., Gordon, D.L and R. T. Marconi. Molecular analyses of the interaction of Borrelia hermsii FhbA with the complement regulatory protein factor H and infection induced antibody.Infect. Immun. 74(4):2007-14. 2006.

Hovis, K.M., Schriefer, ME, Bahlani, S., and R.T. Marconi. Immunological analyses of the Borrelia hermsii factor H/FHL-1 binding protein, FhbA: Demonstration of its utility as a diagnostic marker and epidemiological tool for tick-borne relapsing fever. Infect. Immunity.

Buckles, E, Earnhart, C.G. and R.T. Marconi. Analysis of the antibody response in humans to the type A OspC loop 5 domain and assessment of the potential utility of the loop 5 epitope in Lyme disease vaccine development. Clinical and Vaccine Immunology. In press

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