|
| |
Masayori Inouye |
 |
Distinguished Professor
Department of Biochemistry
UMDNJ-Robert Wood Johnson Medical School
Ph.D., Osaka University
Tel: [732] 235-4115
Fax: [732] 235-4559/4783
inouye@cabm.rutgers.edu
UMDNJ Page |
Toxin-antitoxin (TA) Systems; Their Roles in Bacterial Physiology and the Development of Novel Antibiotics
Almost all bacteria including human pathogens contain suicide or toxin genes, which are induced under stress conditions leading to cell growth arrest and eventual cell death in a way similar to apoptosis or programmed cell death in higher systems. The importance of these toxin genes in medical science was not fully appreciated until recently, when our laboratory and others started to decipher the cellular targets of these toxins and how they inhibit cell growth leading to cell death. Bacterial physiology is considered to be tightly regulated by these toxins and their cognate antitoxins or by the toxin networks under stress conditions. Notably, by taking advantage of the suicidal properties of these toxins, it is possible to develop novel antibiotics against human pathogens. Since Escherichia coli contain more than 13 TA systems, it serves as an ideal paradigm for the study of not only bacterial toxins, but also previously unknown aspects of bacterial physiology governed by the toxin network. Our goal is to decipher structures and functions of the E. coli toxins and study their cellular network. In addition, we are also studying the TA systems in Mycobacterium tuberculosis by identifying their cellular targets and their possible roles in the pathogenecity of this bacterium in human tissues.
Selected Publications
- Zhang, Y., Zhang, J., Hoeflich, K. P., Ikura, M., Qing, G. and Inouye, M. MazF Cleaves Cellular mRNAs Specifically at ACA to Block Protein Synthesis in Escherichia coli. (2003) Mol. Cell, 12, 913-923.
- Zhang, J., Zhang Y., Zhu, L., Suzuki, M. and Inouye, M. Interference of mRNA Function by Sequence-specific Endoribonuclease PemK. (2004) J. Biol. Chem., 279, 20678-20684.
- Zhang, Y., Zhu, L., Zhang, J. and Inouye, M. Characterization of ChpBK, an mRNA Interferase from Escherichia coli. (2005) J. Biol. Chem., 280, 26080-26088.
- Nariya, H. and Inouye, M. MazF, an mRNA Interferase, Mediates Programmed Cell Death during Multicellular Myxococcus Development. (2008) Cell. 132, 55-66.
- Liu, M., Zhang, Y., Inouye, M. and Woychik, W. Bacterial Addiction Module Toxin Doc Inhibits Translation Elongation through its Association with the 30S Ribosome. (2008) Proc. Natl. Acad Sci. USA. 105, 5885-5890.
- Li, G.Y., Zhang, Y., Inouye, M. and Ikura, M. Structural Mechanism of Transcriptional Autorepression of the Escherichia coli RelB/RelE Antitoxin/Toxin Module. (2008) J. Biol. Chem. 380, 107-119.
- Prysak, M. H., Mozdzierz, C., Cook, A. M., Zhu, L., Zhang, Y., Inouye, M. and Woychik, N. A. Bacterial Toxin YafQ is an Endoribonuclease that Associates with the Ribosome and Blocks Translation Elongation through Sequence-specific and Frame-dependent mRNA Cleavage. (2009) Mol. Micro. 71, 1071-1087.
- Zhang, Y. and Inouye, M. The Inhibitory Mechanism of Protein Synthesis by YoeB, an Escherichia coli Toxin. (2009) J. Biol. Chem. 284, 6627-6638.
CABM
Home
Top |