Dai Guofei, Cheng Ni, Dong Lei, Muramatsu Mutsumi, Xiao Shudong, Wang Ming-Wei, Zhu De-Xu
Department of Biochemistry, Nanjing University, Nanjing 210093, P.R. China.
Antimicrob Agents Chemother. 2005 Aug;49(8):3468-73. doi: 10.1128/AAC.49.8.3468-3473.2005.
The antibacterial activities of NE-2001 were tested against 24 clinical isolates of Helicobacter pylori and compared with those of amoxicillin, clarithromycin, metronidazole, and furazolidone. The MIC(50) and MIC(90) of this synthetic compound on the isolates were 8 and 16 mug/ml, respectively. This action was highly selective against Helicobacter pylori; there was a >4-fold difference between the concentration of NE-2001 required to inhibit the growth of Helicobacter pylori and that required to inhibit the growth of common aerobic and anaerobic bacteria. Exposure of Helicobacter pylori (ATCC43504) to NE-2001 at the MIC (4 mug/ml), or at a greater concentration, resulted in an extensive loss of viability. The phenomenon was also observed at pH levels between 3.0 and 7.0. When two clinical Helicobacter pylori strains were successively cultured at subinhibitory concentrations of NE-2001, no significant changes in the bactericidal effects were found. The morphological alterations of Helicobacter pylori cells (ATCC43504), exposed to NE-2001 at various concentrations for 6 h, were observed using transmission electron microcopy. The bacterium displayed features such as swelling, vacuole-like structures in the cytoplasm, and cell destruction following exposure to NE-2001. The efficacy of NE-2001 was maintained when evaluated in eight clinical isolates resistant to metronidazole and five isolates resistant to both metronidazole and clarithromycin (MIC ranging between 4 and 16 mug/ml). The above-described results suggest that NE-2001 may have the potential to be developed as a candidate agent for the treatment of Helicobacter pylori infection.
对NE - 2001针对24株临床分离的幽门螺杆菌的抗菌活性进行了测试，并与阿莫西林、克拉霉素、甲硝唑和呋喃唑酮的抗菌活性进行了比较。该合成化合物对这些分离株的MIC(50)和MIC(90)分别为8微克/毫升和16微克/毫升。这种作用对幽门螺杆菌具有高度选择性；抑制幽门螺杆菌生长所需的NE - 2001浓度与抑制常见需氧菌和厌氧菌生长所需的浓度之间存在4倍以上的差异。将幽门螺杆菌(ATCC43504)暴露于MIC(4微克/毫升)或更高浓度的NE - 2001中，会导致其活力大幅丧失。在pH值为3.0至7.0之间也观察到了这种现象。当两种临床幽门螺杆菌菌株在亚抑制浓度的NE - 2001下连续培养时，未发现杀菌效果有显著变化。使用透射电子显微镜观察了在不同浓度的NE - 2001中暴露6小时的幽门螺杆菌细胞(ATCC43504)的形态变化。暴露于NE - 2001后，该细菌呈现出肿胀、细胞质中出现空泡样结构以及细胞破坏等特征。在8株对甲硝唑耐药的临床分离株和5株对甲硝唑和克拉霉素均耐药的分离株( MIC范围为4至16微克/毫升)中评估时，NE - 2001的疗效得以维持。上述结果表明，NE - 2001可能有潜力被开发成为治疗幽门螺杆菌感染的候选药物。
