文献类型：期刊文献

英文题名：Hormesis Effect of Berberine against Klebsiella pneumoniae Is Mediated by Up-Regulation of the Efflux Pump KmrA

作者：Li, Ying[1];Wen, Honglin[2];Ge, Xizhen[1]

第一作者：李映

通讯作者：Ge, XZ[1]

机构：[1]Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China;[2]Capital Med Univ, Beijing Hosp Tradit Chinese Med, Beijing 100010, Peoples R China

第一机构：北京联合大学生物化学工程学院

通讯机构：[1]corresponding author), Beijing Union Univ, Coll Biochem Engn, Beijing 100023, Peoples R China.|[1141726]北京联合大学生物化学工程学院;[11417]北京联合大学;

年份：2021

卷号：84

期号：11

起止页码：2885-2892

外文期刊名：JOURNAL OF NATURAL PRODUCTS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000723680000012)】；

基金：This work was financially supported by Project of Beijing Municipal Commission of Education [KZ201911417049]; Special Project of Major Science and Technology of Hebei Province [19026517Z]; and Beijing Municipal Education Commission Technology Plan [KM202011417006].

语种：英文

摘要：Berberine (BBR) is an effective drug for human intestinal inflammation by preventing intestinal adhesion of bacterial pathogens, while its antibacterial activity is ineffective. Although the antimicrobial mechanisms of BBR are intensively studied at high concentrations, the response of pathogens to its low concentrations remains poorly understood. Here we demonstrated that low concentrations of BBR (3 and 6 mu g/mL) conferred by hormesis accelerated cell growth of an important Gram-negative pathogen, Klebsiella pneumoniae, in vitro, while higher concentrations (25 and 50 mu g/mL) resulted in the opposite. Transcriptome analysis of K. pneumoniae revealed the up-regulated expression of the KmrA efflux pump and further confirmed it was hypersensitive to BBR stress. Strikingly, when cultivated in tetracycline, the growth-promoting effect of BBR became more significant, while this effect was reversed in the presence of the efflux pump inhibitor cyanide-m-chlorophenylhydrazone. The hormesis was also found in Enterobacter cloacae and Acinetobacter baumannii. More importantly, the presence of BBR at low concentrations resulted in higher minimal inhibitory concentrations of efflux-related antibiotics such as rifampicin and azithromycin. Overall, our data demonstrated the hormesis of BBR and revealed the potential risk of its applications against Gram-negative pathogens at low concentrations.