Identification of a strong and specific antichlamydial N-acylhydrazone.
Identification of a strong and specific antichlamydial N-acylhydrazone.
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DOI：
10.1371/journal.pone.0185783
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Fan H
中科院分区：
文献类型：
--
作者：
Zhang H;Kunadia A;Lin Y;Fondell JD;Seidel D;Fan H
性传播沙眼衣原体是一种非常常见的感染，通常会导致严重的并发症，包括不孕症和盆腔炎综合征。目前有几种广谱抗生素用于治疗C。沙眼虽然有效，但它们也会杀死有益的阴道乳酸杆菌。两种N-酰腙CF 0001和CF 0002先前已显示抑制衣原体生长，而对人细胞和乳杆菌属没有毒性。特别重要的是，导致这些抑制剂耐药的随机突变率似乎极低。在这里，我们报告了CF 0001和CF 0002的三个类似物，对衣原体具有显著更强的抑制作用。尽管新化合物（称为SF 1、SF 2和SF 3）对一种选择为CF 0001耐药性的罕见衣原体变体（Chlamydia muridarum MCR）的抑制效率略有降低，但当使用浓度为75-100 μM时，它们完全克服了耐药性。重要的是，SF 1、SF 2和SF 3对乳酸杆菌没有显示出任何毒性作用，而SF 3也被人类宿主细胞良好耐受。分离SF 3抗性变体的努力是不成功的。相比之下，利福平或壮观霉素耐药的变异体来自较少数量的衣原体。我们的研究结果表明，SF 3利用类似于CF 0001和CF 0002的抗衣原体机制，并且将更难使衣原体产生耐药性，可能使其成为更有效的抗衣原体药物。
Sexually transmitted Chlamydia trachomatis is an extremely common infection and often leads to serious complications including infertility and pelvic inflammatory syndrome. Several broad-spectrum antibiotics are currently used to treat C. trachomatis. Although effective, they also kill beneficial vaginal lactobacilli. Two N-acylhydrazones, CF0001 and CF0002, have been shown previously to inhibit chlamydial growth without toxicity to human cells and Lactobacillus spp. Of particular significance, the rate of random mutation leading to resistance of these inhibitors appears to be extremely low. Here, we report three analogs of CF0001 and CF0002 with significantly stronger inhibitory effects on chlamydiae. Even though the new compounds (termed SF1, SF2 and SF3) displayed slightly decreased inhibition efficiencies for a rare Chlamydia variant selected for CF0001 resistance (Chlamydia muridarum MCR), they completely overcame the resistance when used at concentrations of 75–100 μM. Importantly, SF1, SF2 and SF3 did not shown any toxic effect on lactobacilli, whereas SF3 was also well tolerated by human host cells. An effort to isolate SF3-resistant variants was unsuccessful. By comparison, variants resistant to rifampin or spectinomycin were obtained from smaller numbers of chlamydiae. Our findings suggest that SF3 utilizes an antichlamydial mechanism similar to that of CF0001 and CF0002, and will be more difficult for chlamydiae to develop resistance to, potentially making it a more effective antichlamydial agent.
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DOI：
10.1099/mic.0.049668-0
发表时间：
2011-09
期刊：
Microbiology (Reading, England)
影响因子：
--
作者：
Bao X;Pachikara ND;Oey CB;Balakrishnan A;Westblade LF;Tan M;Chase T;Nickels BE;Fan H
通讯作者：
Fan H
影响因子：
4.4
作者：
Chen, Lili;Lei, Lei;Zhong, Guangming
通讯作者：
Zhong, Guangming
影响因子：
3.7
作者：
Gong Z;Luna Y;Yu P;Fan H
通讯作者：
Fan H
苯亚甲基酰肼以不依赖于 III 型分泌和铁螯合的方式抑制衣原体生长
影响因子：
3.2
作者：
Bao, Xiaofeng;Gylfe, Asa;Fan, Huizhou
通讯作者：
Fan, Huizhou
影响因子：
3.1
作者：
Cotter, TW;Miranpuri, GS;Byrne, GI
通讯作者：
Byrne, GI