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.
Publications
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. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. Sun R, Converse PJ, Ko C, Tyagi S, Morrison NE, Bishai WR. Mycobacterium tuberculosis ECF sigma factor sigC is required for lethality in mice and for the conditional expression of a defined gene set. Mol Microbiol. 2004 Apr;52(1):25-38.
8. Geiman DE, Kaushal D, Ko C, Tyagi S, Manabe YC, Schroeder BG, Fleischmann RD, Morrison NE, Converse PJ, Chen P, Bishai WR. 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. 2004 Mar;72(3):1733-45.
9. Dorman SE, Hatem CL, Tyagi S, Aird K, Lopez-Molina J, Pitt ML, Zook BC,
Dannenberg AM Jr, Bishai WR, Manabe YC. Susceptibility to tuberculosis: clues from studies with inbred and outbred New Zealand White rabbits. Infect Immun. 2004 Mar;72(3):1700-5.
10.Nuermberger EL, Yoshimatsu T, Tyagi S, Bishai WR, Grosset JH. Paucibacillary tuberculosis in mice after prior aerosol immunization with Mycobacterium bovis BCG. Infect Immun. 2004 Feb;72(2):1065-71.
11.Nuermberger EL, Yoshimatsu T, Tyagi S, O'Brien RJ, Vernon AN, Chaisson RE, Bishai WR, Grosset JH. Moxifloxacin-containing regimen greatly reduces time to culture conversion in
murine tuberculosis. Am J Respir Crit Care Med. 2004 Feb 1;169(3):421-6.
12.Manabe YC, Dannenberg AM Jr, Tyagi SK, Hatem CL, Yoder M, Woolwine SC, Zook BC, Pitt ML, Bishai WR. Different strains of Mycobacterium tuberculosis cause various spectrums of disease in the rabbit model of tuberculosis. Infect Immun. 2003 Oct;71(10):6004-11.
13.Sarkar DP, Ramani K, Tyagi SK. Targeted gene delivery by virosomes. Methods Mol Biol. 2002;199:163-73. Review.
14.Kaushal D, Schroeder BG, Tyagi S, Yoshimatsu T, Scott C, Ko C, Carpenter L, Mehrotra J, Manabe YC, Fleischmann RD, Bishai WR. Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative sigma factor, SigH. Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8330-5.
15.Yoshimatsu T, Nuermberger E, Tyagi S, Chaisson R, Bishai W, Grosset J. Bactericidal activity of increasing daily and weekly doses of moxifloxacin in murine tuberculosis. Antimicrob Agents Chemother. 2002 Jun;46(6):1875-9.
16.Kumar M, Hassan MQ, Tyagi SK, Sarkar DP. A 45,000-M(r) glycoprotein in the Sendai virus envelope triggers virus-cell fusion. J Virol. 1997 Sep;71(9):6398-406.
17.Ramani K, Bora RS, Kumar M, Tyagi SK, Sarkar DP. Novel gene delivery to liver cells using engineered virosomes. FEBS Lett. 1997 Mar 10;404(2-3):164-8.
