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  • Title: Isolation and characterization of inhibitors of the essential histidine kinase, YycG in Bacillus subtilis and Staphylococcus aureus.
    Author: Watanabe T, Hashimoto Y, Yamamoto K, Hirao K, Ishihama A, Hino M, Utsumi R.
    Journal: J Antibiot (Tokyo); 2003 Dec; 56(12):1045-52. PubMed ID: 15015732.
    Abstract:
    The set of sensor kinase YycG and response regulator YycF is the only essential two-component system (TCS) in Bacillus subtilis and Staphylococcus aureus. We have developed a screening method for antibacterial agents that inhibit YycG, the essential histidine kinase (HK). To increase screening sensitivity, a temperature-sensitive yycF mutant (CNM2000) of B. subtilis with super-sensitivity to HK inhibitors was constructed, which was used for the screening of acetone extracts from 4000 microbes. A total of 11 samples showed higher sensitivity to CNM2000 than to wild-type parent 168, and seven of those were characterized to be potent inhibitors against autophosphorylation of YycG. One sample compound was purified and identified as aranorosinol B, a known antibacterial agent against Gram-positive bacteria including B. subtilis and S. aureus. Aranorosinol B inhibited YycG from both B. subtilis and S. aureus with a half-maximum inhibitory concentration (IC50) of 223 and 211 microM, respectively.
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