Dr. Janakiram Seshu
210-458-6578 ofc, 210-458-6679 lab
Our research interests focus on two infectious diseases: 1) Lyme Disease and 2) Q fever.
Lyme Disease is the most prevalent arthropod-borne infectious disease in the US. Borrelia burgdorferi, the causative agent of Lyme disease is transmitted to humans (and to other mammals) by the bite of infected ticks. This spirochetal pathogen rapidly alters its gene expression depending on the feeding status of the ticks and upon transmission to mammalian hosts. Our current research interests are directed towards:
1). Determining the role of linear plasmid 54 (lp54) encoded genes of B. burgdorferi in the infectivity of mammalian hosts.
2). Characterization of the mechanisms of interactions of B. burgdorferi with mammalianhost cell surfaces.
3). Regulation of gene expression in B. burgdorferi-determining the contributions of Carbon storage regulator A (CsrABb) in modulating signal-dependent gene expression in B. burgdorferi and its interactions with other borrelial regulators of gene expression.
4). Metabolomics of B. burgdorferi facilitating its adaptation to host-specific conditions.
Q fever is caused by Coxiella burnetii - an obligate, intracellular pathogen. Acute Q fever is a self-limiting flu-like illness and is readily amenable to treatment with antibiotics. Chronic Q fever, on the other hand, is not easily treated with antibiotics and results in endocarditis, hepatitis and pneumonia. C. burnetii with phase I LPS is highly infectious, disseminated as an aerosol, capable of withstanding harsh environmental. C. burnetii resides and replicates within the phagolysosomal vacuoles of macrophages and hence has a unique niche protected from the neutralizing effects of humoral immune response. A potent cell-mediated immunity is required to clear this intracellular acidophile. C. burnetii with phase II LPS is avirulent and serves as an excellent tool to study the intracellular trafficking kinetics of this pathogen using a variety of eukaryotic cells. Our current research efforts are therefore directed towards:
1). Identification of T cell epitopes of C. burnetii
2). Modification of select C. burnetii antigens to enhance protective T cell response against C. burnetii
3). Generation of targeted deletion mutants of Phase II C. burnetii for study intracellular trafficking kinetics in eukaryotic cells/cell lines.
Undergraduate Research Training Program on Biology of Spirochetes and Vector-borne Infectious Diseases
The major goal of this program is to provide intensive hands-on training in experimental methods addressing questions in areas of biology of spirochetes and in other vector-borne infections. The students will perform research on select topics depending on the duration of their undergraduate studies at UTSA. They will learn routine methods such as DNA cloning, isolation of DNA and restriction enzyme analysis, expression and purification of recombinant proteins, generation of plasmid constructs for targeted deletion of genes in bacteria, PCR and quantitative PCR, immunoblot analysis, in vitro and in vivo phenotypic analysis of bacterial strains. The students are trained on critical analysis of experimental data as well as preparing their experimental data for oral and poster presentations. Competitive fellowships are available for interested students.
S. L. Rajasekhar Karna, Rajesh G. Prabhu, Ying-Han Lin, Christine L. Miller and J. Seshu. (2013). Contributions of environmental signals and conserved residues to the functions of Carbon storage regulator A of Borrelia burgdorferi (CsrABb) Infection and Immunity. (in press).
Christine L. Miller; S. L. Rajasekhar Karna; J. Seshu (2013) Borrelia host adaptation Regulator (BadR) regulates rpoS to modulate host adaptation and virulence factors in Borrelia burgdorferi Molecular Microbiology;88(1):105-124.
J. Dafhne Aguirre; Hillary M. Clark; Matthew McIlvin; Christine Vazquez; Shaina L. Palmere; Dennis J. Grab; J. Seshu; P. John Hart; Mak Saito; Valeria C. Culotta. (2013) A manganese-rich environment supports superoxide dismutase activity in a lyme disease pathogen, borrelia burgdorferi Journal of Biological Chemistry;288(12):8468-8478.
Hongyuan Zheng; Andrew Y. Li; Laura J. Fielden; Jingze Liu; Janakiram Seshu; Adalberto A. Pérez de León (2013) Effects of permethrin and amitraz on gas exchange and water loss in unfed adult females of Amblyomma americanum (Acari: Ixodidae) Pesticide Biochemistry and Physiology. 2013.
Arulanandam BP, Lakshmana Chetty S, Yu JJ, Leonard S, Klose KK, Seshu J, Cap A, Valdes JJ, Chambers JP (2012). Francisella DnaK Inhibits Tissue Nonspecific Alkaline Phosphatase. J. Biol Chem. [Epub ahead of print] PMID: 22923614.
Van Laar, Lin YH, Miller CL, Karna SL, Chambers JP and J. Seshu (2012). Effect of Levels of Acetate on the Mevalonate Pathway of Borrelia burgdorferi. PLoS One 7(5):e38171 PMID: 22748043
Karna, S-L. R., E. Sanjuan, M. D. Esteve-Gassent, C .L. Miller, M. Maruskova and J. Seshu*. (2011) CsrABb modulates levels of lipoproteins and key regulators of gene expression (RpoS and BosR) critical for pathogenic mechanisms of Borrelia burgdorferi. Infect. Immun. 79:732-744. PMID: 21078860.
*Article of significant interest selected from Feb 2011 issue of Infection & Immunity by editors.
B. V. Subba Raju, Maria. D. Esteve-Gassent1, S. L. Rajasekhar Karna, Christine L. Miller, Tricia A. Van Laar and J. Seshu (2011). Oligopeptide permease A5 (OppA5, BBA34) modulates vertebrate host-specific adaptation of Borrelia burgdorferi. Infect.Immun.79:3407-3420. PMID: 21628523.
Murthy AK, Li W, Chaganty BK, Kamalakaran S, Guentzel MN, Seshu J, Forsthuber TG, Zhong G, Arulanandam BP . (2011). Tumor necrosis factor alpha production from CD8+ T cells mediates oviduct pathological sequelae following primary genital Chlamydia muridarum infection. Infect. Immun. 79(7):2928-35.
Nallaparaju KC, Yu JJ, Rodriguez SA, Zogaj X, Manam S, Guentzel MN, Seshu J, Murthy AK, Chambers JP, Klose KE, Arulanandam BP.(2011)Evasion of IFN-γ signaling by Francisella novicida is dependent upon Francisella outer membrane protein C. PLoS One. 6(3):e18201.
Li W, Murthy AK, Chaganty BK, Guentzel MN, Seshu J, Chambers JP, Zhong G, Arulanandam BP.(2011)Immunization with dendritic cells pulsed ex vivo with recombinant chlamydial protease-like activity factor induces protective immunity against genital chlamydiamuridarum challenge. Front Immunol. 2:73.
Rajasekhar Karna S. L., Zogaj, X., Barker, J.R., Seshu, J., Dove, S.L. and Klose, K. E. (2010). A bacterial two-hybrid system that utilizes Gateway cloning for rapid screening of protein-protein interactions. Biotechniques 49:831-833
Li W., Murthy A.K., Guentzel M.N., Chambers J.P., Forsthuber T.G., Seshu J., Zhong G, Arulanandam B.P. (2010). Immunization with a combination of integral chlamydial antigens and a defined secreted protein induces robust immunity against genital chlamydial challenge. Infection Immunity 78:3942-3949.
Eva Sanjuan, Maria D. Esteve-Gassent, Mahulena Maruskova and J. Seshu (2009). Overexpression of BbCsrA (BB0184) alters morphology and antigen profiles of Borrelia burgdorferi. Infection and Immunity 77:5149-5162
Cong Y., J-J Yu, M. N. Guentzel, M. T. Berton, J. Seshu, K. E. Klose and B. Arulanandam (2009). Vaccination with a defined Francisella tularensis subsp. novicida pathogenecity island mutant (DiglB) induces protective immunity against homotypic and heterotypic challenge. Vaccine. (In Press).
Murthy A.K., B.K. R. Chaganty, W. Li, M. N. Guentzel, J. P. Chambers, J. Seshu, G. Zhong and B. P. Arulanandam (2009). A Limited Role for Antibody in Protective Immunity Induced by rCPAF and CpG Vaccination Against Primary Genital Chlamydia muridarum Challenge FEMS Microbiol Immunol. 55: 271-279
Esteve-Gassent, M.D., Elliott, N and J. Seshu (2009). sodA is essential for virulence of Borrelia burgdorferi in the murine model of Lyme disease. Mol. Microbiol. 71:594-612
Maruskova, M and J. Seshu (2008). Deletion of BBA64, BBA65 and BBA66 does not alter the infectivity phenotype of Borrelia burgdorferi in the murine model of Lyme disease. Infect. Immun. 76: 5274-84.
Li, W., A.K. Murthy, M. N. Guentzel, J. Seshu, G. Zhong, B. P. Arulanandam (2008). IFN-g from Antigen Specific CD4+ T cells is Required and Quantitatively Sufficient to Induce Anti-Chlamydial Protective Immunity. J. Immunol. 180:3375-3382
Mahulena Maruskova, M. Dolores Esteve-Gassent, Valerie L. Sexton and J. Seshu (2008). The role of bba64 locus of Borrelia burgdorferi in early stages of infectivity in the murine model of Lyme disease. Infect. Immun. 76: 391-402.
Li, W., M. N. Guentzel, J. Seshu, G. Zhong, A.K. Murthy and B. P. Arulanandam (2007). Targeted Multi-Subunit Vaccination Approach to Evaluate Cross-Serovar Protection against Genital Chlamydial Infection. Clin. Vaccine. Immunol. 14: 1537-1544