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Judith W. Zyskind 


Professor Emeritus
Department of Biology
Molecular Biology Institute
Ph.D., Iowa State University

Discovering Antibiotic Targets

A major human health problem in the area of infectious diseases is the alarming increase in resistance to antibiotics in bacterial pathogens, where some pathogens have become resistant to all antibiotics.  Because antibiotics target the products of essential genes, screening for previously unknown essential genes can lead to the development of novel and effective antibiotic drugs.  There are estimated to be at least 400 essential proteins in each bacterial species, leaving 385 unexplored proteins that could serve as targets for the development of new antibiotics.  Identifying these proteins in pathogenic organisms is of great interest to the pharmaceutical industry because they encode potential antibiotic targets.  Most of the approaches used currently for identifying new antibiotic targets from genomic information or genetic screening are time consuming and labor intensive.  My lab discovered a novel, extremely rapid method for identifying antibiotic targets in pathogenic bacteria.  This discovery led to the commerialization of the technology and the formation of Elitra Pharmaceuticals, Inc.  See http://www.elitra.com/our_profile/

Representative Publications:

    Chiaramello, A. E., and Zyskind, J. W. (1990) Coupling of DNA replication to growth rate in Escherichia coli: a possible role for guanosine tetraphosphate. J. Bacteriol. 172:2013-2019.

    Mahaffy, J. M., and Zyskind, J. W. (1990) A comparison of two models for initiation of replication in Escherichia coli. Proceedings of the Second International Conference on Mathematical Population Dynamics, Marcel Dekker, p. 747-765.

    Smith, D. W., Stine, W. B., Svitil, A. L., Bakker, A., and Zyskind, J. W. (1992) Escherichia coli cells lacking methylation-blocking factor/leucine-responsive regulatory protein have precise timing of initiation of DNA replication in the cell cycle. J. Bacteriol. 174:3078-3082.

    Zyskind, J. W., Svitil, A. L., Stine, W. B., Biery, M. C., and Smith, D. W. (1992) RecA protein of Escherichia coli and chromosome partitioning. Mol. Microbiol. 6:2525-2537.

    Zyskind, J. W., and Smith, D. W. (1992) DNA replication, the bacterial cell cycle, and cell growth. Cell 69:5-8.

    Svitil, A. L., Cashel, M. and Zyskind, J. W. (1993) Guanosine tetraphosphate (ppGpp) inhibits protein synthesis in vivo: a possible protective mechanism for starvation stress. J. Biol. Chem. 268:2307-2311.

    Thomas, P. M., Golly, K. F., Zyskind, J. W., and Virginia, R. A. (1994) Variation of clonal, mesquite-associated rhizobial and bradyrhizobial populations from surface and deep soils by symbiotic gene region restriction fragment length polymorphism and plasmid profile analysis. App. Environ. Microbiol. 60: 1146-1153.

    Thomas, P. M., Golly, K. F., Virginia, R. A., and Zyskind, J. W. (1995) Cloning of mesquite rhizobial and bradyrhizobial nod gene regions and nucleotide sequence of the mesquite rhizobial nodD gene. App. Environ. Microbiol. 61:3422-3429.

    Froelich, J., Phuong, T. and Zyskind, J. W. (1996) Fis binding in the dnaA operon promoter region. J. Bacteriol. 20:6006-6012.

    Kalabat, D., Froelich, J.,.Phuong, T., Forsyth, R. A., Newman, V. G., and Zyskind, J. W. (1998) Chitobiase, a new reporter enzyme. BioTechniques 25:1030-1035.

    Molina, F., Jiménez-Sánchez, A., Zyskind, J. W., and Guzmán, E. C. (1999) Chromosomal insertions localized around oriC affect the cell cycle in Escherichia coli. Biochimie 81:811-818.

    G. C., K., Ozcan, F., Guzmán, E. C., Smith, D. W., Newman, V. G., and Zyskind, J. W. (2000) Role of DNA methylation at GATC sites in the dnaA promoter, dnaAp2. J. Mol. Microbiol. Biotechnol. 2:301-310.

    Zyskind, J. W. (2000) Recombinant DNA-basic procedures.  In Encyclopedia of Microbiology, Vol. 4, 2nd Ed. J. Lederberg, ed. (Academic Press, San Diego), pp. 55-64.

    Zyskind, J. W., and Smith, D. W. (2001) Ori sequences. In Encyclopedia of Genetics, Vol. 4, S. Brenner and J. Miller, eds. (Academic Press, San Diego), pp. 1381-1387.

    Haselbeck, R., Wall, D., Jiang, B., Ketela, T., Zyskind, J., Bussey, H., Foulkes, J. G., and Roemer, T. (2002). Comprehensive essential gene identification as a platform for novel anti-infective drug discovery. Current Pharm. Design 8:99-110.

    Forsyth, R. A., Haselbeck, R. J., Ohlsen, K. L., Yamamoto, R. T.,  Xu, H., Trawick, J. D., Wall, D., Wang, L., Brown-Driver, V., Froelich, J. M, G. C., K., King, P., McCarthy, M., Malone, C., Misiner, B., Robbins, D., Tan, Z., Zhu, Z, Carr, G., Mosca, D., Zamudio, C., Foulkes, J. G., and Zyskind, J. W. (2002) A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol. Microbiol. 43:1387-1400.  Also, see cover of this issue 43(6).

    Grigorian, A. V., Lustig, R. B., Guzmán, E. C., Mahaffy, J. M., and Zyskind, J. W. (2003)  Escherichia coli cells with increased levels of DnaA and deficient in recombinational repair have decreased viability. J. Bacteriol. 185:630-644.

Patents and Applications:
    Zyskind, J. W. and Forsyth, R. A. Method for Identifying Microbial Proliferation Genes, issued May 8, 2001, U.S. Patent # 6,228,579.

    Zyskind, J. W., Ohlsen, K. L., Trawick, J., Forsyth, R. A., Froelich, J. M., Carr, G. J., Yamamoto, R. T., Xu, H. H. Genes Identified as Required for Proliferation in Escherichia coli.  Intenational patent application Publication No. WO 00/44906.

    Zyskind, J. W. Chitobiase as a Reporter Enzyme. USA patent application filed.

    Zyskind, J. W. Use of Ectoenzymes and Secreted Enzymes to Monitor Cellular Proliferation. USA and PCT (International) patent applications filed.

Note: Entrez Medline entries for a particular Author name may correspond with multiple authors with the same initials. Also, the list is limited to entries stored in the Entrez Medline Database and may not accurately reflect the true number of publications