Yang Weifeng, Wei Qing, Tong Qian, Cui Kaiyu, He Gaiying, Lin Longfei, Ma Lvyan Z, Cornelis Pierre, Wang Yi
Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China.
Department of Food and Environmental Sciences, University of Helsinki, Helsinki, Finland.
Front Microbiol. 2020 Dec 17;11:517462. doi: 10.3389/fmicb.2020.517462. eCollection 2020.
is an opportunistic pathogen that can infect a wide variety of hosts including humans, plants, and animals. The production of virulence factors is the determinant of the infection paradigm and is under orchestrated regulation via cell-to-cell communication process called quorum sensing (QS). To disable QS circuits and prevent bacterial infections, a large battery of anti-QS agents, particularly from traditional Chinese medicine have been developed. Here, we used as a model microorganism to investigate the effect of traditional Chinese medicine Tanreqing (TRQ) formula on bacterial pathogenicity. Phenotypic analysis showed that TRQ treatment could completely inhibit the production of phenazine pyocyanin and moderately inhibit the production of virulence factors such as rhamnolipids, elastase, and alkaline protease. Further transcriptomic analyses revealed that TRQ treatment could significantly attenuate the expression of QS-regulated genes in and TRQ-treated regulon shared a large overlap with QS regulon. Component contribution to QS inhibition shed light on the indispensable role of all five components in TRQ formula. Further genetic analysis indicated that upstream regulators of QS systems, including two-component systems GacS/GacA and PprA/PprB, were both inhibited by TRQ treatment. Finally, our TRQ formula could efficiently protect from killing by . Altogether, we have proved TRQ formula as an effective and specific agent to attenuate bacterial virulence and combat bacterial infections.
是一种机会致病菌,可感染包括人类、植物和动物在内的多种宿主。毒力因子的产生是感染模式的决定因素,并通过称为群体感应(QS)的细胞间通讯过程受到精心调控。为了破坏QS回路并预防细菌感染,已经开发了大量的抗QS剂,特别是来自中药的抗QS剂。在这里,我们以作为模式微生物来研究中药痰热清(TRQ)配方对细菌致病性的影响。表型分析表明,TRQ处理可完全抑制吩嗪绿脓菌素的产生,并适度抑制鼠李糖脂、弹性蛋白酶和碱性蛋白酶等毒力因子的产生。进一步的转录组分析表明,TRQ处理可显著减弱中QS调控基因的表达,并且TRQ处理的调控子与QS调控子有很大的重叠。成分对QS抑制的贡献揭示了TRQ配方中所有五种成分的不可或缺的作用。进一步的遗传分析表明,QS系统的上游调节因子,包括双组分系统GacS/GacA和PprA/PprB,均受到TRQ处理的抑制。最后,我们的TRQ配方可以有效地保护免受的杀伤。总之,我们已经证明TRQ配方是一种有效且特异性的减弱细菌毒力和对抗细菌感染的药物。