Working on the evaluation of new drugs and vaccines for TB chemotherapy in animal models.
Current research work involves:
- Antimicrobial drugs evaluation in mouse model.
Under this project, I am working with the development of a potent antimicrobial drug regimen to reduce the course of TB chemotherapy. The main aim of this project is to reduce the time duration of treatment by the addition and or substitution of the existing drug by a new flouroquinilone, Moxifloxacin. The pharmacokinetics / pharmacodynamics of the drug has already been tested and published by our lab.
- Development of Rabbit Model of Vaccine testing
Different live attenuated mycobacterium strains are being tested in this model to find out the most efficacious vaccine against tuberculosis. Live attenuated bacteria lacking some virulence gene are being administered in rabbits through different routes. After 9 weeks of vaccination, efficacy of potential candidate strain is measured in terms of tubercles formation in the lungs of the rabbit by a virulent bacillus.
- Virulence testing in Mouse Model
Gene knockout strains of virulent TB are being tested for the lack of pathogenesis in this animal model of tuberculosis. We are using different mouse strains to test the survival or the phenotypic difference of the strain.
To read some of these publications online, click here. Please note that to read the full text of some of these articles requires that you have an online subscription to the journal.
1. Makarov, V., G. Manina, K. Mikusova, U. Mollmann, O. Ryabova, B. Saint-Joanis, N. Dhar, M. R. Pasca, S. Buroni, A. P. Lucarelli, A. Milano, E. De Rossi, M. Belanova, A. Bobovska, P. Dianiskova, J. Kordulakova, C. Sala, E. Fullam, P. Schneider, J. D. McKinney, P. Brodin, T. Christophe, S. Waddell, P. Butcher, J. Albrethsen, I. Rosenkrands, R. Brosch, V. Nandi, S. Bharath, S. Gaonkar, R. K. Shandil, V. Balasubramanian, T. Balganesh, S. Tyagi, J. Grosset, G. Riccardi, and S. T. Cole. 2009. Benzothiazinones Kill Mycobacterium tuberculosis by Blocking Arabinan Synthesis. Science 324:801-4
2. Williams, K. N., C. K. Stover, T. Zhu, R. Tasneen, S. Tyagi, J. H. Grosset, and E. Nuermberger. 2009. Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model. Antimicrob Agents Chemother 53:1314-9.
3. Tasneen, R., S. Tyagi, K. Williams, J. Grosset, and E. Nuermberger. 2008. Enhanced bactericidal activity of rifampin and/or pyrazinamide when combined with PA-824 in a murine model of tuberculosis. Antimicrob Agents Chemother 52:3664-8.
4. Nuermberger, E., S. Tyagi, R. Tasneen, K. N. Williams, D. Almeida, I. Rosenthal, and J. H. Grosset. 2008. Powerful bactericidal and sterilizing activity of a regimen containing PA-824, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. Antimicrob Agents Chemother 52:1522-4.
5. Be, N. A., G. Lamichhane, J. Grosset, S. Tyagi, Q. J. Cheng, K. S. Kim, W. R. Bishai, and S. K. Jain. 2008. Murine model to study the invasion and survival of Mycobacterium tuberculosis in the central nervous system. J Infect Dis 198:1520-8.
6. Rosenthal, I. M., M. Zhang, K. N. Williams, C. A. Peloquin, S. Tyagi, A. A. Vernon, W. R. Bishai, R. E. Chaisson, J. H. Grosset, and E. L. Nuermberger. 2007. Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. PLoS Med 4:e344.
7. Agarwal, N., S. C. Woolwine, S. Tyagi, and W. R. Bishai. 2007. Characterization of the Mycobacterium tuberculosis sigma factor SigM by assessment of virulence and identification of SigM-dependent genes. Infect Immun 75:452-61.
8. Rosenthal, I. M., K. Williams, S. Tyagi, C. A. Peloquin, A. A. Vernon, W. R. Bishai, J. H. Grosset, and E. L. Nuermberger. 2006. Potent twice-weekly rifapentine-containing regimens in murine tuberculosis. Am J Respir Crit Care Med 174:94-101.
9. Nuermberger, E., I. Rosenthal, S. Tyagi, K. N. Williams, D. Almeida, C. A. Peloquin, W. R. Bishai, and J. H. Grosset. 2006. Combination chemotherapy with the nitroimidazopyran PA-824 and first-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother 50:2621-5.
10. Lamichhane, G., T. R. Raghunand, N. E. Morrison, S. C. Woolwine, S. Tyagi, K. Kandavelou, and W. R. Bishai. 2006. Deletion of a Mycobacterium tuberculosis proteasomal ATPase homologue gene produces a slow-growing strain that persists in host tissues. J Infect Dis 194:1233-40.
11. Tyagi, S., E. Nuermberger, T. Yoshimatsu, K. Williams, I. Rosenthal, N. Lounis, W. Bishai, and J. Grosset. 2005. Bactericidal activity of the nitroimidazopyran PA-824 in a murine model of tuberculosis. Antimicrob Agents Chemother 49:2289-93.
12. Rosenthal, I. M., K. Williams, S. Tyagi, A. A. Vernon, C. A. Peloquin, W. R. Bishai, J. H. Grosset, and E. L. Nuermberger. 2005. Weekly moxifloxacin and rifapentine is more active than the denver regimen in murine tuberculosis. Am J Respir Crit Care Med 172:1457-62.
13. Nuermberger, E.,S. Tyagi, K.N. Williams, I. Rosenthal, W. R. Bishai, and J. H. Grosset. 2005. Rifapentine, moxifloxacin, or DNA vaccine improves treatment of latent tuberculosis in a mouse model. Am J Respir Crit Care Med 172:1452-6.
14. Lamichhane, G., S. Tyagi, and W. R. Bishai. 2005. Designer arrays for defined mutant analysis to detect genes essential for survival of Mycobacterium tuberculosis in mouse lungs. Infect Immun 73:2533-40.
15. Calamita, H., C. Ko, S. Tyagi, T. Yoshimatsu, N. E. Morrison, and W. R. Bishai. 2005. The Mycobacterium tuberculosis SigD sigma factor controls the expression of ribosome-associated gene products in stationary phase and is required for full virulence. Cell Microbiol 7:233-44.
16. Sun, R., P. J. Converse, C. Ko, S. Tyagi, N. E. Morrison, and W. R. Bishai. 2004. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol Microbiol 52:25-38.
17. Nuermberger, E. L., T. Yoshimatsu, S. Tyagi, K. Williams, I. Rosenthal, R. J. O'Brien, A. A. Vernon, R. E. Chaisson, W. R. Bishai, and J. H. Grosset. 2004. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am J Respir Crit Care Med 170:1131-4.
18. Nuermberger, E. L., T. Yoshimatsu, S. Tyagi, R. J. O'Brien, A. N. Vernon, R. E. Chaisson, W. R. Bishai, and J. H. Grosset. 2004. Moxifloxacin-containing regimen greatly reduces time to culture conversion in murine tuberculosis. Am J Respir Crit Care Med 169:421-6.
19. Nuermberger, E. L., T. Yoshimatsu, S. Tyagi, W. R. Bishai, and J. H. Grosset. 2004. Paucibacillary tuberculosis in mice after prior aerosol immunization with Mycobacterium bovis BCG. Infect Immun 72:1065-71.
20. Geiman, D. E., D. Kaushal, C. Ko, S. Tyagi, Y. C. Manabe, B. G. Schroeder, R. D. Fleischmann, N. E. Morrison, P. J. Converse, P. Chen, and W. R. Bishai. 2004. Attenuation of late-stage disease in mice infected by the Mycobacterium tuberculosis mutant lacking the SigF alternate sigma factor and identification of SigF-dependent genes by microarray analysis. Infect Immun 72:1733-45.
21. Dorman, S. E., C. L. Hatem, S. Tyagi, K. Aird, J. Lopez-Molina, M. L. Pitt, B. C. Zook, A. M. Dannenberg, Jr., W. R. Bishai, and Y. C. Manabe. 2004. Susceptibility to tuberculosis: clues from studies with inbred and outbred New Zealand White rabbits. Infect Immun 72:1700-5.
22. Manabe, Y. C., A. M. Dannenberg, Jr., S. K. Tyagi, C. L. Hatem, M. Yoder, S. C. Woolwine, B. C. Zook, M. L. Pitt, and W. R. Bishai. 2003. Different strains of Mycobacterium tuberculosis cause various spectrums of disease in the rabbit model of tuberculosis. Infect Immun 71:6004-11.
23. Yoshimatsu, T., E. Nuermberger, S. Tyagi, R. Chaisson, W. Bishai, and J. Grosset. 2002. Bactericidal activity of increasing daily and weekly doses of moxifloxacin in murine tuberculosis. Antimicrob Agents Chemother 46:1875-9.
24. Sarkar, D. P., K. Ramani, and S. K. Tyagi. 2002. Targeted gene delivery by virosomes. Methods Mol Biol 199:163-73.
25. Kaushal, D., B. G. Schroeder, S. Tyagi, T. Yoshimatsu, C. Scott, C. Ko, L. Carpenter, J. Mehrotra, Y. C. Manabe, R. D. Fleischmann, and W. R. Bishai. 2002. Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative sigma factor, SigH. Proc Natl Acad Sci U S A 99:8330-5.
26. Ramani, K., R. S. Bora, M. Kumar, S. K. Tyagi, and D. P. Sarkar. 1997. Novel gene delivery to liver cells using engineered virosomes. FEBS Lett 404:164-8.
27. Kumar, M., M. Q. Hassan, S. K. Tyagi, and D. P. Sarkar. 1997. A 45,000-M(r) glycoprotein in the Sendai virus envelope triggers virus-cell fusion. J Virol 71:6398-406.