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白藜芦醇通过下调 AdeB 外排泵来恢复对碳青霉烯类耐药鲍曼不动杆菌的氯己定活性。

Rescued chlorhexidine activity by resveratrol against carbapenem-resistant Acinetobacter baumannii via down-regulation of AdeB efflux pump.

机构信息

Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Antimicrobial Resistance and Stewardship Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

出版信息

PLoS One. 2020 Dec 2;15(12):e0243082. doi: 10.1371/journal.pone.0243082. eCollection 2020.

DOI:10.1371/journal.pone.0243082
PMID:33264338
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7710055/
Abstract

The aim of this study was to determine the activity and synergistic mechanisms of resveratrol in combination with chlorhexidine against carbapenem-resistant Acinetobacter baumannii clinical isolates. The activity of resveratrol plus antimicrobial agents was determined by checkerboard and time-kill assay against carbapenem-resistant A. baumannii isolated from patients at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Overexpression of efflux pumps that mediates chlorhexidine susceptibility was characterized by the ethidium bromide accumulation assay. The effect of resveratrol on the expression of efflux pump genes (adeB, adeJ, adeG abeS, and aceI) and the two-component regulators, adeR and adeS was determined by RT-qPCR. The combination of resveratrol and chlorhexidine resulted in strong synergistic and bactericidal activity against carbapenem-resistant A. baumannii. Up-regulation of adeB and aceI was induced by chlorhexidine. However, the addition of resveratrol increased chlorhexidine susceptibility with increased intracellular accumulation of ethidium bromide in A. baumannii indicating that resveratrol acts as an efflux pump inhibitor. Expression of adeB was significantly reduced in the combination of resveratrol with chlorhexidine indicating that resveratrol inhibits the AdeB efflux pump and restores chlorhexidine effect on A. baumannii. In conclusion, reduced adeB expression in A. baumannii was mediated by resveratrol suggesting that AdeB efflux pump inhibition contributes to the synergistic mechanism of resveratrol with chlorhexidine. Our finding highlights the potential importance of resveratrol in clinical applications.

摘要

本研究旨在确定白藜芦醇与洗必泰联合应用对耐碳青霉烯鲍曼不动杆菌临床分离株的活性和协同机制。通过棋盘和时间杀伤试验，测定来自泰国曼谷朱拉隆功国王纪念医院患者的耐碳青霉烯鲍曼不动杆菌分离株对白藜芦醇加抗菌药物的活性。采用溴化乙锭积累试验对介导洗必泰敏感性的外排泵过表达进行特征分析。通过 RT-qPCR 测定白藜芦醇对外排泵基因（adeB、adeJ、adeG abeS 和 aceI）和两个组件调节剂 adeR 和 adeS 的表达的影响。白藜芦醇与洗必泰联合应用对耐碳青霉烯鲍曼不动杆菌具有强烈的协同和杀菌活性。洗必泰诱导 adeB 和 aceI 的上调。然而，白藜芦醇的加入增加了 A. baumannii 中溴化乙锭的细胞内积累，从而增加了洗必泰的敏感性，表明白藜芦醇作为外排泵抑制剂。在白藜芦醇与洗必泰联合应用中，adeB 的表达显著降低，表明白藜芦醇抑制 AdeB 外排泵并恢复了洗必泰对 A. baumannii 的作用。总之，A. baumannii 中 adeB 表达的降低是由白藜芦醇介导的，这表明 AdeB 外排泵抑制有助于白藜芦醇与洗必泰的协同作用机制。我们的发现强调了白藜芦醇在临床应用中的潜在重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/2d2fcfd52160/pone.0243082.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/0b38e2cb8459/pone.0243082.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/af49731b15aa/pone.0243082.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/cd6b15e8b58f/pone.0243082.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/850b83491d3f/pone.0243082.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/2d2fcfd52160/pone.0243082.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/0b38e2cb8459/pone.0243082.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/af49731b15aa/pone.0243082.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/cd6b15e8b58f/pone.0243082.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/850b83491d3f/pone.0243082.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90dc/7710055/2d2fcfd52160/pone.0243082.g005.jpg

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