New target for inhibition of bacterial RNA polymerase: 'switch region'

Aashish Srivastava, Meliza Talaue, Shuang Liu, David Degen, Richard Y. Ebright, Elena Sineva, Anirban Chakraborty, Sergey Y. Druzhinin, Sujoy Chatterjee, Jayanta Mukhopadhyay, Yon W. Ebright, Alex Zozula, Juan Shen, Sonali Sengupta, Rui Rong Niedfeldt, Cai Xin, Takushi Kaneko, Herbert Irschik, Rolf Jansen, Stefano DonadioNancy Connell, Richard H. Ebright

Research output: Contribution to journalReview article

92 Scopus citations

Abstract

A new drug target - the 'switch region' - has been identified within bacterial RNA polymerase (RNAP), the enzyme that mediates bacterial RNA synthesis. The new target serves as the binding site for compounds that inhibit bacterial RNA synthesis and kill bacteria. Since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. Since the new target is different from targets of other antibacterial agents, compounds that bind to the new target are not cross-resistant with other antibacterial agents. Four antibiotics that function through the new target have been identified: myxopyronin, corallopyronin, ripostatin, and lipiarmycin. This review summarizes the switch region, switch-region inhibitors, and implications for antibacterial drug discovery.

Original languageEnglish (US)
Pages (from-to)532-543
Number of pages12
JournalCurrent Opinion in Microbiology
Volume14
Issue number5
DOIs
StatePublished - Oct 1 2011

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All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Srivastava, A., Talaue, M., Liu, S., Degen, D., Ebright, R. Y., Sineva, E., Chakraborty, A., Druzhinin, S. Y., Chatterjee, S., Mukhopadhyay, J., Ebright, Y. W., Zozula, A., Shen, J., Sengupta, S., Niedfeldt, R. R., Xin, C., Kaneko, T., Irschik, H., Jansen, R., ... Ebright, R. H. (2011). New target for inhibition of bacterial RNA polymerase: 'switch region'. Current Opinion in Microbiology, 14(5), 532-543. https://doi.org/10.1016/j.mib.2011.07.030