J.K. Bhattacharjee
Professor of Microbiology
Research Interests:
Research project in my laboratory deals with the DNA sequence analysis and the application of unique lysine genes for the rapid detection and control of pathogenic yeast. Lysine is an essential amino acid (obtained from diet) for humans and animals. However, it is synthesized by two mutually exclusive pathways in bacteria, fungi, and plants. Bacteria, plants, and certain phycomycetes use the diaminopimelic acid pathway, whereas the yeasts and other higher fungi use the α-aminoadipate pathway for the biosynthesis of lysine. Genetic and biochemical analysis of lysine auxotrophs of Saccharomyces cerevisiae have confirmed eight enzyme steps and more than 12 unlinked genes responsible for the α-aminoadipate pathway. One of the enzymes, α-aminoadipate-reductase, of this pathway catalyzes the conversion of α-aminoadipic acid to α-aminoadipic-semialdehyde in the presence of ATP, Mg2+, CoA, and NADPH. Functions of two unlinked genes (LYS2 and LYS5) are required for this highly complex reaction.
Candida albicans is the major yeast infection of AIDS, cancer, and transplant patients. There is urgent need to develop rapid and sensitive detection method and specific targets for antifungal drugs. Ideal targets are molecules which are present only in fungal pathogens and absent in human hosts. The exclusive nature of the α-aminoadipic acid pathway in fungi makes the genes and enzymes of this pathway attractive targets for detection probes and drugs. We are currently investigating the structure and function of selected lysine genes (LYS2 and LYS5) from S. cerevisiae and C. albicans. The Lys5p in the presence of CoA activates Lys2p which in turn in the presence of ATP and NADPH converts α-aminoadipate to α-aminoadipic-semialdehyde. We are employing PCR generated mutations of conserved amino acid residues and performing biochemical characterization of novel functional domains of Lys2p and Lys5p. Results of this investigation would provide much needed basic knowledge of the mechanism of this unique and complex enzymatic reaction. Well characterized novel functional domains could also serve as potential targets for the PCR detection and antifungal drugs.
Current Projects:
Current research emphasis is on:- cloning, molecular characterization, and transcriptional regulation of specific lysine genes,
- use of novel lysine genes for the rapid detection of C. albicans and other pathogenic fungi, and
- structure-function studies of the Lys2p and Lys5p in the unique posttranslational activation of α-aminoadipate reductase enzyme.
We have received three U.S. Patents based on novel DNA sequences of the cloned lysine genes as potential targets for rapid molecular (PCR) identification of the opportunistic fungal pathogen Candida albicans. We have also published several research papers on the structural and functional properties of the novel LYS2 and LYS5 genes of C. albicans.
U.S. Patents:
- Jnanendra K. Bhattacharjee, Richard Garrad, Paul Skatrud and Robert Perry. Methods and reagents for detecting fungal pathogens in a biological sample, 22 claims. U.S. Patent no. 5,919,617, awarded July 6, 1999.
- Jnanendra K. Bhattacharjee and Vasker Bhattacherjee. Methods and reagents for detecting fungal pathogens in a biological sample, 24 claims. U.S. Patent no. 5,910,409, awarded June 8, 1999.
- Jnanendra K. Bhattacharjee, Kalavati Suvarna and Vasker Bhattacherjee. Reagents and kits for detecting fungal pathogens in a biological sample, 16 claims. U.S. Patent no. 6,455,248 B1, awarded Sept. 24, 2002.
Selected Publications:
- Guo, S., S.A. Evans, M.B. Wilkes, and J.K. Bhattacharjee. 2001. Novel posttranslational activation of the LYS2-encoded α-aminoadipate reductase for biosynthesis of lysine and site-directed mutational analysis of conserved amino acid residues in the activation domain of Candida albicans. J. Bacteriol. 183:7120-7125.
- Guo, S. and J.K. Bhattacharjee. 2003. Site-directed mutational analysis of the novel catalytic domains of α-aminoadipate reductase (Lys2p) from Candida albicans. Mol. Gen. Genomics. 269:271-279.
- Guo, S., and J.K. Bhattacharjee. 2003. Molecular characterization of the Candida albicans LYS5 gene and site-directed mutational analysis of the PPTase (Lys5p) domains for lysine biosynthesis. FEMS Microbiology Letters 224:261-267.
- Bhattacharjee, J.K., G.R. Janssen and T.G. Gregg. A Teaching Guide to Evoluation. The Science Teacher, 70:24-31.
Emeriti Faculty: Bhattacharjee