亚MIC剂量的抗生素对艰难梭菌tcdC、tcdE、tcdR转录的影响

目的亚最小抑菌浓度(MIC)剂量的某些抗生素能够诱导和促进艰难梭菌毒力编码基因及其毒素的表达,但具体机制不明。本文从艰难梭菌的毒力调控基因(tcdC、tcdE、tcdR)着手来试图解释亚MIC剂量的抗生素对艰难梭菌毒力编码基因和毒素的影响。方法中国株艰难梭菌BJ08分别生长在含有1/2 MIC剂量的克雷霉素或头孢噻肟或无抗生素的脑心浸液肉汤(BHI)液体培养基中。每4h,取一定量的艰难梭菌,通过实时荧光定量PCR检测其毒力调控基因(tcdC、tcdE、tcdR)mRNA的表达。结果 BJ08在1/2 MIC剂量的克雷霉素存在的情况下,对毒力调控基因mRNA表达的影响不大;但是在1/2 MIC剂量的头孢噻肟存在的情况下,tcdCmRNA的表达在培养早期和中期低于对照组,tcdE和tcdR的表达比起对照组都增高且提前,但两者增加幅度不同,高峰期也不同。结论在某些亚MIC剂量的抗生素存在的情况下,艰难梭菌毒力编码基因和毒素表达的变化可能是通过调节调控基因而实现的。

Effect of sub MIC antibiotics on transcriptions of tcdC,tcdE and tcdR genes of Clostridium difficile

objective To investigate the expression of virulence genes and toxins induced and promoted with subminimum inhibitory concentration（MIC） of certain antibiotics by mRNA expressions of virulence regulatory genes includingtcdC, tcdEand tcdR genes.Methods StrainBJ08 isolated in China was grown with and without 1/2-MIC concentrations ofClindamycin or Cefotaxime. Real-time PCR was used to detect the level of tcdC, tcdE andtcdRmRNA every 4 h.Result There was little effect on level of tcdC, tcdE and tcdR mRNA in the presence of 1/2 MIC concentration of clindamycin. But thelevel of tcdC was lower in the prophase and metaphase of cultivation, and the level of tcdE and tcdR was higher and earlier thanthose of antibiotic-free control group in the presence of 1/2 MIC concentration of cefotaxime. The effects varied in augmentalmagnitude and peak stage. Conclusion This experiments have proved the change of expression of toxic genes may beregulated by virulence regulatory genes in the presence of sub MIC concentration of antibiotics.