Journal
CURRENT OPINION IN MICROBIOLOGY
Volume 14, Issue 5, Pages 532-543Publisher
CURRENT BIOLOGY LTD
DOI: 10.1016/j.mib.2011.07.030
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Funding
- NIH [GM41376, AI072766, AI90837]
- Global Alliance for TB Drug Development contract
- Howard Hughes Medical Institute
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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.
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