Varalakshmi D. Vissa
Associate Professor
Phone: 491-0752, 491-4139
Fax: 491-6396
Email:
Varalakshmi.Vissa@ColoState.EDU
Office: B212A Microbiology Building
Lab: B218, B228 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 University).
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.
Selected Publications
Pub Med for Vissa VD.
Sakamuri RM, Kimura M, Li Wei, Kim H-C, Lee H-Y, Madanahally K, Black IV WC, Balagon M, Gelber R, Cho S-N, Brennan PJ and Vissa V. 2009. Population based molecular epidemiology of leprosy in Cebu, Philippines. J Clin Microbiol. 47:2844-2854.
Kimura M, Sakamuri RM, Groathouse NA, Rivoire BL, Gingrich D, Krueger-Koplin S, Cho SN, Brennan PJ, and Vissa V. 2009. Rapid variable-number tandem-repeat genotyping for Mycobacterium leprae clinical specimens. J Clin Microbiol. 47:1757-1766.
Kaur D, Pham H, Larrouy-Maumus G, Rivière M, Vissa V, Guerin ME, Puzo G, Brennan PJ, and Jackson M. 2009. Initiation of methylglucose lipopolysaccharide biosynthesis in mycobacteria. PLoS ONE. 4:e5447.
Vissa V, Sakamuri RM, Li Wei, and Brennan PJ. 2009. Defining mycobacteria: Shared and specific genome features for different lifestyles. Indian J of Microbiol.49: 11-47.
Martinez LR, Harris B, Black WC 4th, Meyer RM, Brennan PJ, Vissa VD, Jones RL. 2008. Genotyping North American animal Mycobacterium bovis isolates using multilocus variable number tandem repeat analysis. J Vet Diagn Invest. 20:707-715.
Hernández E, Cardona-Castro N, Rodríguez G, Villegas S, Beltrán C, Kimura M, Vissa VD, and Gómez Y. 2008. [Study of rifampin and dapsone resistance in three patients with recurring leprosy]. Rev Panam Salud Publica. 23:73-77.
Oskam L, Dockrell HM, Brennan PJ, Gillis T, Vissa V, Richardus JH; IDEAL Consortium. 2008. Molecular methods for distinguishing between relapse and reinfection in leprosy. Trop. Med. Int. Health. 13:1325-1326.
Weng X., Z. Wang, J. Liu, M. Kimura, W.C. Black 4th, P.J. Brennan, H. Li, V.D. Vissa. 2007. Identification and distribution of Mycobacterium leprae genotypes in a region of high leprosy prevalence in China: a 3-Year molecular epidemiological study. J. Clin. Microbiol. 45:1728-1734.
Kaur D., S. Berg, P. Dinadayala, B. Gicquel, D. Chatterjee, M. R. McNeil, V. D. Vissa, D. C. Crick, M. Jackson, and P. J. Brennan. 2006. Biosynthesis of mycobacterial lipoarabinomannan: role of a branching mannosyltransferase. Proc. Natl. Acad. Sci. U S A. 103:13664-13669.
Dinadayala P., D. Kaur, S. Berg, A.G. Amin, V.D. Vissa, D. Chatterjee, P.J. Brennan, D.C. Crick. 2006. Genetic basis for the synthesis of the immunomodulatory mannose caps of lipoarabinomannan in Mycobacterium tuberculosis. J. Biol. Chem. 281:20027-20035.
Shi L., S. Berg, A. Lee, J.S. Spencer, J. Zhang, V. Vissa, M.R. McNeil, K.H. Khoo, and D. Chatterjee. 2006. The carboxy terminus of EmbC from Mycobacterium smegmatis mediates chain length extension of the Arabinan in lipoarabinomannan. J Biol Chem. 281:19512-19526.
Berg, S., J. Starbuck, J.B. Torrelles, V.D. Vissa, D.C. Crick, D. Chatterjee, and P.J. Brennan. 2005. Roles of conserved praline and glycosyltransferase motifs of EmbC in biosynthesis of lipoarabinomannan. J. Biol. Chem. 280:5651-5663.
Mills, J.A., K. Motichka, M. Jucker, H.P. Wu, B.C. Uhlik, R.J. Stern, M.S. Scherman, V.D. Vissa, F. Pan, M. Kundu, and M. McNeil. 2004. Inactivation of the mycobacterial rhamnosyltransferase, which is needed for the formation of the arabinogalactan-peptidoglycan linker, leads to irreversible loss of viability. J. Biol Chem. 279:43540-43546.
Groathouse, N.A., B. Rivoire, H. Kim, H. Lee, S. N. Cho, P. J. Brennan, and V.D. Vissa. 2004. Multiple polymorphic loci for molecular typing of Mycobacterium leprae strains. J. Clin. Microbiol. 42:1666-1672.
Ronning D.R., V. Vissa, G.S. Besra, J.T. Belisle, and J.C. Sacchettini. 2004. Mycobacterium tuberculosis antigen 85A and 85C structures confirm binding orientation and conserved substrate specificity. J Biol. Chem. 279:36771-36777.
Vissa, V.D., and P.J. Brennan. 2001. The genome of Mycobacterium leprae: a minimal mycobacterial gene set. Genome Biology. 2:1-7.
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.