1887

Journal of Medical Microbiology logo

Volume 61, Issue 9

Discovery of a compound that acts as a bacterial PyrG (CTP synthase) inhibitor Free

Abstract

PyrG (CTP synthase) catalyses the conversion of UTP to CTP, an essential step in the pyrimidine metabolic pathway in a variety of bacteria, including those causing community-acquired respiratory tract infections (RTIs). In this study, a luminescence-based ATPase assay of PyrG was developed and used to evaluate the inhibitory activity of 2-(3-[3-oxo-1,2-benzisothiazol-2(3)-yl]phenylsulfonylamino) benzoic acid (compound G1). Compound G1 inhibited PyrG derived from with a 50 % inhibitory concentration value of 0.091 µM, and the inhibitory activity of compound G1 was 13 times higher than that of acivicin (1.2 µM), an established PyrG inhibitor. The results of saturation transfer difference analysis using nuclear magnetic resonance spectroscopy suggested that these compounds compete with ATP and/or UTP for binding to PyrG. Finally, compound G1 was shown to have antimicrobial activity against several different bacteria causing RTIs, such as and , suggesting that it is a prototype chemical compound that could be harnessed as an antimicrobial drug with a novel structure to target bacterial PyrG.

  • Received:
  • Accepted:
  • Published Online:
© 2012 SGM
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2012-09-01
2024-04-26
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Discovery of a compound that acts as a bacterial PyrG (CTP synthase) inhibitor
J. Med. Microbiol. 61, 1280 (2012); https://doi.org/10.1099/jmm.0.046052-0
/content/journal/jmm/10.1099/jmm.0.046052-0
/content/journal/jmm/10.1099/jmm.0.046052-0
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