1. Academic Validation
  2. Clostridium difficile DNA polymerase IIIC: basis for activity of antibacterial compounds

Clostridium difficile DNA polymerase IIIC: basis for activity of antibacterial compounds

  • Curr Enzym Inhib. 2011 Oct;7(3):147-153. doi: 10.2174/157340811798807597.
Andrea Torti 1 Andrea Lossani Lida Savi Federico Focher George Edward Wright Neal Curtis Brown Wei-Chu Xu
Affiliations

Affiliation

  • 1 Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, I-27100 Pavia, Italy.
Abstract

Based on the finding that aerobic Gram-positive antibacterials that inhibit DNA polymerase IIIC (pol IIIC) were potent inhibitors of the growth of anaerobic Clostridium difficile (CD) strains, we chose to clone and express the gene for pol IIIC from this organism. The properties of the recombinant Enzyme are similar to those of related pol IIICs from Gram-positive aerobes, e.g. B. subtilis. Inhibitors of the CD Enzyme also inhibited B. subtilis pol IIIC, and were competitive with respect to the cognate substrate 2'-deoxyguanosine 5'-triphosphate (dGTP). Significantly, several of these inhibitors of the CD pol IIIC had potent activity against the growth of CD clinical isolates in culture.

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