Varalakshmi D. Vissa
Assistant Professor

Phone: 491-0752
Fax: 491-6396
Email: Varalakshmi.Vissa@ColoState.EDU
Office: B308 Microbiology Building
Lab: C310 Microbiology Building
Links: Leprosy Research Support

 

Degrees

• M.Sc. Biochemistry: University of Madras, India
• Ph. D. Biochemistry: University of Maryland, Baltimore

Research Interests

Leprosy Research

• Although leprosy has been successfully controlled by global implementation of multidrug therapy since 1982, the disease has yet to be eradicated. In 2002 alone, 620, 672 new cases of leprosy were detected in the highly endemic countries, as reported by the World Health Organization (http://www.who.int/lep/).
• What are the measures and challenges that remain in the efforts to eliminate leprosy? As a member of the Leprosy research group at CSU, founded and headed by Dr. Patrick J. Brennan, there are several topics of research and clinical interest in our laboratory.
• Leprosy is caused by the organism Mycobacterium leprae. Despite the fact that
  M. leprae was identified in 1873, and is the first human pathogen discovered, a few fundamental factors constrain leprosy research in a laboratory. M. leprae is an obligate intracellular pathogen with a doubling time of 12-14 days even in a susceptible host. Furthermore, there aren't any methods available for in vitro cultivation and genetic manipulation of the M. leprae organism.
• However, a major turning point in 2001 was the revelation of the genome sequence (http://www.sanger.ac.uk/Projects/M_leprae/) and the recognition that the M. leprae genome has downsized by extreme gene decay processes, to nearly half that of a related species, M. tuberculosis. A second resource has been the availability of viable M. leprae from infected nude mice from our NIH-NIAID partner/collaborator (Dr. James Krahenbuhl at National Hansen's Disease Laboratory, Louisiana State Univeristy).
• The approaches in our laboratory entail exploring and exploiting the M. leprae genome to develop reagents and techniques for application in a leprosy clinical setting. We utilize molecular methods for strain typing (DNA fingerprinting) and detection of drug resistance. We are also interested in furthering basic knowledge with regard to the limited proteome and its impact on the physiology of M. leprae. Theses studies will ultimately influence development of vaccines, diagnostics and in vitro cultivation.

Cell wall biogenesis in mycobacteria.

• The cell wall of mycobacteria has been a focus of research at the Mycobacteria Research Laboratories (MRL). The unusual composition and assembly of the cell wall affect survival and pathogenicity of the mycobacteria, while also providing targets for the detection and diagnosis of infection.
• A component of research in our laboratory is comparing the genome sequences of several different species of mycobacteria for the identification of candidate genes involved in the biosynthesis of common key structural macromolecules, as well as species-specific antigenic molecules in cell walls. In partnership with other faculty at MRL, the functions of the genes are validated by a variety of genetic and biochemical methods.

Selected Publications

Pub Med for Vissa VD.

• Vissa, V.D., and P.J. Brennan. 2002. Impact of the Mycobacterium leprae genome sequence on leprosy research. In Genomics of GC Rich Gram-Positive Bacteria. Caister Academic Press, Wymondham, U.K.; pp. 85-118.
• Kaur, D., T.L. Lowary, V.D. Vissa, D.C. Crick, and P.J. Brennan. 2002. Characterization of the epitope of anti-lipoarabinomannan antibodies as the terminal hexaarabinofuranosyl motif of mycobacterial arabinans. Microbiology 148: 3049-3057.
• Brennan, P.J., and V.D. Vissa. 2001. Genomic evidence for the retention of the essential mycobacterial cell wall in the otherwise defective Mycobacterium leprae. Lepr. Rev. 72: 415-428.
• Vissa, V.D., and P.J. Brennan. 2001. The genome of Mycobacterium leprae: a minimal mycobacterial gene set. Genome Biology 2: 1?7.
• Ronning, D.R., T. Klabunde, G.S. Besra, V.D. Vissa, J.T. Belisle, and J.C. Sacchettini. 2000. Crystal structure of the secreted form of antigen 85C reveals potential targets for mycobacterial drugs and vaccines. Nat. Struct. Biol. 7: 141-146.
• Samanich, K.M., M.A. Keen, V.D. Vissa, J.D. Harder, J.S. Spencer, J.T. Belisle, S. Zolla-Pazner, S. Laal. 2000. Serodiagnostic potential of culture filtrate antigens of Mycobacterium tuberculosis. Clin. Diagn. Lab. Immunol. 7: 662-668.
• Stern, R.J., T-Y. Lee, T-J. Lee, W. Yan, M.S. Scherman, V.D. Vissa, S-K. Kim, B.L. Wanner, and M.R. McNeil. 1999. Conversion of dTDP-4-keto-6-Deoxyglucose to free dTDP-4-keto-Rhamnose by the rmlC gene products of Escherichia coli and Mycobacterium tuberculosis. Microbiology 145: 663-671.
• Ma, Y., J.A. Mills, J.T. Belisle, V. Vissa, M. Howell, K. Bowlin, M.S. Scherman, and M. McNeil. 1997. Determination of the pathway for rhamnose biosynthesis in mycobacteria: cloning, sequencing and expression of the Mycobacterium tuberculosis gene encoding a-D-glucose-1-phosphate thymidylyltransferase. Microbiology 143: 937-945.
• Belisle, J.T., V.D. Vissa, T. Sievert, K. Takayama, P.J. Brennan, and G.S. Besra. 1997. Role of the major antigen of Mycobacterium tuberculosis in cell wall biogenesis. Science 276: 1420-1422.
• Varalakshmi Desiaju, W.G. Shanbruch, and A.-L. Lu. 1993. Nucleotide sequence of the Salmonella typhimurium mutB Gene, the homolog of Escherichia coli mutY. J. Bacteriol. 175: 541-543.