Discovering

INDIVIDUAL RESEARCHER

Chandra Shekhar Bakshi , D.V.M. , Ph.D.
Research Assistant Professor
e-mail: bakshis@mail.amc.edu

Education

1989 - D.V.M. from College of Veterinary Sc. & A.H., Jabalpur, India
1998 - Ph.D. from Indian Veterinary Research Institute, India

Current Research

Our long-term research goal is to understand the molecular bases of bacterial infections and the use of such knowledge in the development of better and effective vaccines. The focus of our research is on Francisella tularensis, a category A biothreat agent. Our research efforts are directed towards understanding F. tularensis pathogenesis in the perspective of host-pathogen interactions. In addition, our laboratory also focuses on the role of adjuvants such as IL-12 in the induction of mucosal immunity against respiratory pathogens. By taking a comprehensive approach in the areas of immunology and bacterial genetics, we are aiming to identify virulence determinants of F. tularensis and understand critical aspects of the host's immune response to this important human pathogen. Our laboratory has made significant progress towards defining the virulence mechanisms of F. tularensis. This research owes much of its success to the refinement of methodologies in our laboratory to genetically manipulate F. tularensis. We have generated a mutant deficient in superoxide dismutase-B (sodB) gene of F. tularensis. The sodB gene encodes an iron containing SOD (FeSOD) and is important for dismutation of superoxide anions generated during aerobic growth or respiratory burst induced by macrophages consequent to the bacterial entry in these cells. The sodB mutant is hypersensitive to oxidative stress and attenuated for virulence in mice. We are testing efficacy of this mutant as a vaccine candidate in the prevention of respiratory tularemia. We also intend to identify genes involved in the survival of this important pathogen inside immune cells. Identification of specific virulence factors will advance our understanding of tularemia pathogenesis and facilitate development of a safe and efficacious vaccine.

References

1. Bakshi, C.S., Malik, M., Regan, K., Melendez, J.A., Metzger, D.W., Pavlov, V.M. and Sellati, T.J. Superoxide dismutase-B (sodB) deficient mutants of Francisella tularensis demonstrate hypersensitivity to oxidative stress and attenuated virulence. J. Bacteriol. 188 (17): 6443-6448, 2006.



2. Malik, M., Bakshi, C.S., McCabe, K., Catlett, S.V., Singh, R., Metzger, D.W., Melendez, J.A. and Sellati, T.J. Matrix Metalloproteinase 9 (MMP-9) Activity Enhances Host Susceptibility to Pulmonary Infection with Type A and B strains of Francisella tularensis. J. Immunol. 178 (2). 1013-1020, 2007.



3. Bakshi C. S., M. Malik. M. Mahawar, G. S. Kirimanjeswara, K. R. Hazlett, L. E. Palmer, M. B. Furie, J. A. Melendez, T. J. Sellati and D. W. Metzger. An improved vaccine for prevention of respiratory tularemia caused by Francisella tularensis SchuS4 strain. Vaccine, 26: 5276-5288, 2008



4. Mahawar, M., G. S. Kirimanjeswara, D. W. Metzger and C. S. Bakshi. Contribution of citrulline ureidase to Francisella tularensis strain SchuS4 pathogenesis. J. Bacteriol. (15):4798-806,2009



5. Melillo, A. M., M. Mahawar, T. J. Sellati, M. Malik, D. W. Metzger, J. A. Melendez and C. S. Bakshi.Identification of Francisella tularensis live vaccine strain CuZn superoxide dismutase as critical for resistance to extracellular generated reactive oxygen species. 1: J Bacteriol. 2009 Aug 14. [Epub ahead of print]