Torti Andrea, Lossani Andrea, Savi Lida, Focher Federico, Wright George Edward, Brown Neal Curtis, Xu Wei-Chu
Istituto di Genetica Molecolare, Consiglio Nazionale delle Ricerche, I-27100 Pavia, Italy.
Curr Enzym Inhib. 2011 Oct;7(3):147-153. doi: 10.2174/157340811798807597.
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.
基于抑制DNA聚合酶IIIC（pol IIIC）的需氧革兰氏阳性抗菌剂是艰难梭状芽孢杆菌（CD）厌氧菌株生长的有效抑制剂这一发现，我们选择克隆并表达该生物体中pol IIIC的基因。重组酶的特性与革兰氏阳性需氧菌（如枯草芽孢杆菌）中相关的pol IIIC相似。CD酶的抑制剂也抑制枯草芽孢杆菌的pol IIIC，并且相对于同源底物2'-脱氧鸟苷5'-三磷酸（dGTP）具有竞争性。值得注意的是，这些CD pol IIIC抑制剂中的几种对培养中的CD临床分离株的生长具有强效活性。
