鱼腥草素钠抑制铜绿假单胞菌致病相关运动能力的研究

Sodium houttuyfonate inhibits virulence related motility of Pseudomonas aeruginosa

鱼腥草素钠(sodium houttuyfonate,SH)是一种有效抑制致病菌感染的传统中药鱼腥草的活性成分的衍生物,但其抑菌机制尚没有被阐明。本研究通过铜绿假单胞菌运动能力试验发现,SH可在有效抑制与细菌致病性相关的浮泳运动、蹭行运动和集群运动能力。平板分析法实验结果表明24 h内SH对浮泳运动、蹭行运动和48 h内SH对集群运动的抑制趋势呈现显著的浓度依赖性特点;并且在1倍SH最小抑菌浓度(minimum inhibitory concentration,MIC)(512 mg·L^(-1))条件下,细菌的运动能力和阳性对照阿奇霉素(1倍MIC 16 mg·L^(-1))样基本丧失。进一步,基因表达分析发现SH显著抑制铜绿假单胞菌的鞭毛和菌毛结构基因flgB和pilG的表达,提示SH抑制细菌运动能力的可能机制是通过抑制细菌运动相关的特殊结构鞭毛和菌毛的合成而产生。因此,该研究结果首次证明SH可有效抑制细菌的运动能力,并探讨了抑制机制,为该药物在临床上治疗条件性致病菌铜绿假单胞菌提供理论依据。

Sodium houttuyfonate （SH） is a derivative of effective component of a Chinese material medica, Houttuynia cordata, which is applied in anti-infection of microorganism. But, the antimicrobial mechanisms of SH still remain unclear. Here, we firstly discovered that SH effectively inhibits the three types of virulence related motility of Pseudomonas aeruginosa, i. e. , swimming, twitching and swarming. The plate assay results showed that the inhibitory action of SH against swimming and twitching in 24 h and swarming in 48 h is dose-dependent ; and bacteria nearly lost all of the motile activities under the concentration of 1 × minimum inhibitory concentration （MIC） （512 mg · L-1 ） same as azithromycin positive group （1 x MIC, 16 mg· L-1 ）. Furthermore, we found that the expression of structural gene flgB and pilG is down-regulated by SH, which implies that inhibitory mechanism of SH against motility of P. aeruginosa may be due to the inhibition of flagel- la and pili bioformation of P. aeruginosa by SH. Therefore, our presented results firstly demonstrate that SH effectively inhibits the motility activities of P. aeruginosa, and suggest that SH could be a promising antipseudomonas agents in clinic.