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鲍曼不动杆菌中EmrAB外排泵对黏菌素耐药性的作用

Contribution of EmrAB efflux pumps to colistin resistance in Acinetobacter baumannii.

作者信息

Lin Ming-Feng, Lin Yun-You, Lan Chung-Yu

机构信息

Department of Medicine, National Taiwan University Hospital Chu-Tung Branch, Hsin-Chu County, Taiwan.

Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsin-Chu City, Taiwan.

出版信息

J Microbiol. 2017 Feb;55(2):130-136. doi: 10.1007/s12275-017-6408-5. Epub 2017 Jan 26.

DOI:10.1007/s12275-017-6408-5
PMID:28120193
Abstract

Efflux pumps play an important role in antimicrobial resistance for Acinetobacter baumannii. However, the function of the Emr pump system and the relationship between Emr and drug resistance has not been characterized in A. baumannii. In this study, four possible groups of emr-like genes were found by searching a genome database. Among them, A1S_1772 (emrB) and A1S_1773 (emrA) were demonstrated to be co-transcribed as a single operon. Moreover, during osmotic stress, A1S_1772 showed the largest change in gene expression compared to the other emrB-like genes, and deletion of A1S_1772 (AB ΔemrB) significantly slowed cell growth in 20% sucrose. Using a phenotypic microarray analysis, the AB ΔemrB mutant was more susceptible to colistin and nafcillin, paromomycin, spiramycin, and D,L-serine hydroxmate than the wild type. The spot assay, time kill assay and minimal inhibition concentration determination also indicated that the wild type could tolerate colistin better than the AB ΔemrB mutant. Finally, the increased expression levels of all emrB-like genes, including A1S_0775, A1S_0909, A1S_1772, and A1S_1799, in colistin resistance-induced A. baumannii further supported the possible involvement of the emrB genes in A. baumannii colistin resistance. Together, the Emr pump systems in A. baumannii contribute to adaptation to osmotic stress and resistance to colistin.

摘要

外排泵在鲍曼不动杆菌的抗菌耐药性中发挥着重要作用。然而,Emr泵系统的功能以及Emr与耐药性之间的关系在鲍曼不动杆菌中尚未得到表征。在本研究中,通过搜索基因组数据库发现了四组可能的类emr基因。其中,A1S_1772(emrB)和A1S_1773(emrA)被证明作为一个单一操纵子共同转录。此外,在渗透胁迫期间,与其他类emrB基因相比,A1S_1772的基因表达变化最大,并且缺失A1S_1772(AB ΔemrB)显著减缓了在20%蔗糖中的细胞生长。使用表型微阵列分析,AB ΔemrB突变体比野生型对黏菌素、萘夫西林、巴龙霉素、螺旋霉素和D,L-丝氨酸异羟肟酸盐更敏感。点滴试验、时间杀菌试验和最低抑菌浓度测定也表明野生型比AB ΔemrB突变体更能耐受黏菌素。最后,在黏菌素耐药诱导的鲍曼不动杆菌中,包括A1S_0775、A1S_0909、A1S_1772和A1S_1799在内的所有类emrB基因表达水平的增加进一步支持了emrB基因可能参与鲍曼不动杆菌对黏菌素的耐药性。总之,鲍曼不动杆菌中的Emr泵系统有助于适应渗透胁迫和对黏菌素的耐药性。

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PLoS One. 2015 Jul 10;10(7):e0132843. doi: 10.1371/journal.pone.0132843. eCollection 2015.
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Colistin, mechanisms and prevalence of resistance.黏菌素、耐药机制及耐药率
Curr Med Res Opin. 2015 Apr;31(4):707-21. doi: 10.1185/03007995.2015.1018989. Epub 2015 Mar 19.
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Antimicrobial resistance in Acinetobacter baumannii: From bench to bedside.
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Colistin Resistance Mechanism and Management Strategies of Colistin-Resistant Infections.黏菌素耐药机制及耐黏菌素感染的管理策略
Pathogens. 2024 Nov 28;13(12):1049. doi: 10.3390/pathogens13121049.
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Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin.双氯芬酸使多重耐药鲍曼不动杆菌对黏菌素敏感。
PLoS Pathog. 2024 Nov 21;20(11):e1012705. doi: 10.1371/journal.ppat.1012705. eCollection 2024 Nov.
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Alteration in the Morphological and Transcriptomic Profiles of after Exposure to Colistin.暴露于黏菌素后[具体对象]的形态学和转录组学特征改变。 (注:原文中“of”后面缺少具体内容)
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Insertion sequence ISAba11 is involved in colistin resistance and loss of lipopolysaccharide in Acinetobacter baumannii.插入序列 ISAba11 参与鲍曼不动杆菌的多粘菌素耐药和脂多糖丢失。
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