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鲍曼不动杆菌群体感应信号分子诱导耐药基因的表达。

Acinetobacter baumannii quorum-sensing signalling molecule induces the expression of drug-resistance genes.

作者信息

Dou Yi, Song Fei, Guo Feng, Zhou Zengding, Zhu Cailian, Xiang Jun, Huan Jingning

机构信息

Department of Burns and Plastic Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China.

The Ninth People's Hospital, School of Stomatology, Shanghai Jiaotong University, Shanghai Research Institute of Stomatology, Shanghai 200011, P.R. China.

出版信息

Mol Med Rep. 2017 Jun;15(6):4061-4068. doi: 10.3892/mmr.2017.6528. Epub 2017 Apr 28.

Abstract

Quorum-sensing signalling molecules such as N‑acyl homoserine lactones (AHLs) enable certain Gram‑negative bacteria to respond to environmental changes through behaviours, such as biofilm formation and flagellar movement. The present study aimed to identify Acinetobacter baumannii AHLs and assess their influence on antibiotic resistance. A clinical isolate of A. baumannii strain S (AbS) was collected from the wound of a burn patient and high‑performance liquid chromatography and tandem quadrupole or quadrupole time‑of‑flight high‑resolution mass spectrometry was used to identify AbS AHLs. Antibiotic sensitivity was assessed in an AHL‑deficient AbS mutant (AbS‑M), and the expression of drug-resistance genes in the presence of meropenem in AbS, AbS‑M and AbS‑M treated with the AHL N-3-hydroxy-dodecanoyl-homoserine lactone (N‑3‑OH‑C12‑HSL). AbS‑M was more sensitive to meropenem and piperacillin than wild‑type AbS, but resistance was restored by supplementation with N‑3‑OH‑C12‑HSL. In addition, meropenem‑treated AbS‑M expressed lower levels of the drug‑resistance genes oxacillinase 51, AmpC, AdeA and AdeB; treatment with N‑3‑OH‑C12‑HSL also restored the expression of these genes. Overall, the results of the present study indicate that N‑3‑OH‑C12‑HSL may be involved in regulating the expression of drug‑resistance genes in A. baumannii. Therefore, this quorum‑sensing signalling molecule may be an important target for treating multidrug‑resistant A. baumannii infections.

摘要

群体感应信号分子,如N-酰基高丝氨酸内酯(AHLs),使某些革兰氏阴性菌能够通过生物膜形成和鞭毛运动等行为对环境变化做出反应。本研究旨在鉴定鲍曼不动杆菌的AHLs,并评估它们对抗生素耐药性的影响。从一名烧伤患者的伤口收集了鲍曼不动杆菌菌株S(AbS)的临床分离株,并用高效液相色谱和串联四极杆或四极杆飞行时间高分辨率质谱法鉴定AbS的AHLs。在AHL缺陷型AbS突变体(AbS-M)中评估抗生素敏感性,并在美罗培南存在的情况下,检测AbS、AbS-M以及用AHL N-3-羟基十二烷酰高丝氨酸内酯(N-3-OH-C12-HSL)处理的AbS-M中耐药基因的表达。AbS-M比野生型AbS对美罗培南和哌拉西林更敏感,但补充N-3-OH-C12-HSL后耐药性恢复。此外,用美罗培南处理的AbS-M中耐药基因青霉素酶51、AmpC、AdeA和AdeB的表达水平较低;用N-3-OH-C12-HSL处理也恢复了这些基因的表达。总体而言,本研究结果表明,N-3-OH-C12-HSL可能参与调节鲍曼不动杆菌中耐药基因的表达。因此,这种群体感应信号分子可能是治疗多重耐药鲍曼不动杆菌感染的重要靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/583d/5436197/2d2a6256f157/MMR-15-06-4061-g00.jpg

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