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临床鲍曼不动杆菌分离株引起的生物膜形成与AdeFGH外排泵的过表达有关。

Biofilm Formation Caused by Clinical Acinetobacter baumannii Isolates Is Associated with Overexpression of the AdeFGH Efflux Pump.

作者信息

He Xinlong, Lu Feng, Yuan Fenglai, Jiang Donglin, Zhao Peng, Zhu Jie, Cheng Huali, Cao Jun, Lu Guozhong

机构信息

The Third People's Hospital of Wuxi, Wuxi, Jiangsu Province, People's Republic of China.

Jiangsu Institute of Parasitic Diseases, Key Laboratory of Parasitic Disease Control and Prevention (Ministry of Health), Jiangsu Provincial Key Laboratory of Parasite Molecular Biology, Wuxi, Jiangsu Province, People's Republic of China.

出版信息

Antimicrob Agents Chemother. 2015 Aug;59(8):4817-25. doi: 10.1128/AAC.00877-15. Epub 2015 Jun 1.

DOI:10.1128/AAC.00877-15
PMID:26033730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4505227/
Abstract

Chronic wound infections are associated with biofilm formation, which in turn has been correlated with drug resistance. However, the mechanism by which bacteria form biofilms in clinical environments is not clearly understood. This study was designed to investigate the biofilm formation potency of Acinetobacter baumannii and the potential association of biofilm formation with genes encoding efflux pumps, quorum-sensing regulators, and outer membrane proteins. A total of 48 clinically isolated A. baumannii strains, identified by enterobacterial repetitive intergenic consensus (ERIC)-PCR as types A-II, A-III, and A-IV, were analyzed. Three representative strains, which were designated A. baumannii ABR2, ABR11, and ABS17, were used to evaluate antimicrobial susceptibility, biofilm inducibility, and gene transcription (abaI, adeB, adeG, adeJ, carO, and ompA). A significant increase in the MICs of different classes of antibiotics was observed in the biofilm cells. The formation of a biofilm was significantly induced in all the representative strains exposed to levofloxacin. The levels of gene transcription varied between bacterial genotypes, antibiotics, and antibiotic concentrations. The upregulation of adeG correlated with biofilm induction. The consistent upregulation of adeG and abaI was detected in A-III-type A. baumannii in response to levofloxacin and meropenem (1/8 to 1/2× the MIC), conditions which resulted in the greatest extent of biofilm induction. This study demonstrates a potential role of the AdeFGH efflux pump in the synthesis and transport of autoinducer molecules during biofilm formation, suggesting a link between low-dose antimicrobial therapy and a high risk of biofilm infections caused by A. baumannii. This study provides useful information for the development of antibiofilm strategies.

摘要

慢性伤口感染与生物膜形成有关,而生物膜形成又与耐药性相关。然而,细菌在临床环境中形成生物膜的机制尚不清楚。本研究旨在调查鲍曼不动杆菌的生物膜形成能力,以及生物膜形成与编码外排泵、群体感应调节因子和外膜蛋白的基因之间的潜在关联。共分析了48株临床分离的鲍曼不动杆菌菌株,通过肠杆菌重复基因间共识(ERIC)-PCR鉴定为A-II型、A-III型和A-IV型。使用三株代表性菌株,分别命名为鲍曼不动杆菌ABR2、ABR11和ABS17,来评估抗菌药物敏感性、生物膜诱导性和基因转录(abaI、adeB、adeG、adeJ、carO和ompA)。在生物膜细胞中观察到不同类抗生素的最低抑菌浓度(MIC)显著增加。在所有暴露于左氧氟沙星的代表性菌株中,生物膜形成均被显著诱导。基因转录水平因细菌基因型、抗生素和抗生素浓度而异。adeG的上调与生物膜诱导相关。在A-III型鲍曼不动杆菌中,检测到adeG和abaI在左氧氟沙星和美罗培南(1/8至1/2×MIC)作用下持续上调,这些条件导致了最大程度的生物膜诱导。本研究证明了AdeFGH外排泵在生物膜形成过程中自诱导分子合成和运输中的潜在作用,提示低剂量抗菌治疗与鲍曼不动杆菌引起的生物膜感染高风险之间存在联系。本研究为抗生物膜策略的开发提供了有用信息。

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