Clostridium difficile DNA Polymerase IIIC: Basis for Activity of Anti-Bacterial Compounds

Author(s): Andrea Torti, Andrea Lossani, Lida Savi, Federico Focher, George E. Wright, Neal C. Brown, Wei-Chu Xu

Journal Name: Current Enzyme Inhibition

Volume 7 , Issue 3 , 2011

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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.

Keywords: Antibacterials, C. difficile, competitive inhibitors, DNA polymerase, replication, Gram-positive aerobes, B. subtilis, vancomycin, SDS-polyacrylamide gel electrophoresis, morpholinyl derivatives

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Article Details

Year: 2011
Page: [147 - 153]
Pages: 7
DOI: 10.2174/157340811798807597
Price: $65

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