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MexAB-OprM 和 MexXY-OprM 外排泵以及 1 类整合子在烧伤和重症监护病房铜绿假单胞菌对抗生素耐药中的作用。

Role of MexAB-OprM and MexXY-OprM efflux pumps and class 1 integrons in resistance to antibiotics in burn and Intensive Care Unit isolates of Pseudomonas aeruginosa.

机构信息

Department of Medical Microbiology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Islamic Republic of Iran; Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.

Drug Applied Research Center, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.

出版信息

J Infect Public Health. 2018 May-Jun;11(3):364-372. doi: 10.1016/j.jiph.2017.09.016. Epub 2017 Oct 6.

Abstract

BACKGROUND

The overexpression of efflux pumps and existence of class 1 integrons are the most important mechanisms that contribute to antimicrobial resistance in Pseudomonas aeruginosa especially in burn and Intensive Care Units (ICUs). The present study evaluated the role of MexAB-OprM and MexXY-OprM efflux pumps and class 1 integrons in resistance to antibiotics in burn and ICU isolates of P. aeruginosa.

METHODS

Fifteen burn and forty-two ICU isolates were obtained from four hospitals in Northwest Iran. The isolates were identified and evaluated by the disk diffusion and agar dilution methods for determining antibiotic resistances. The presence of class 1 integrons and associated resistance gene cassettes were detected by PCR and sequencing of the products. The expression levels of efflux pumps were evaluated by phenotypic and genotypic (Quantitative Real-time PCR) methods. The isolates were genotyped by Random Amplified Polymorphic DNA Typing (RAPD-PCR).

RESULTS

All burn isolates were integron positive and Multi-drug resistant (MDR), while 78.5% and 69% of ICU isolates were found as MDR and integron positive, respectively. The aadB gene was the most prevalent gene cassette (63.6%) followed by aacA4 (47.7%). Thirty-nine (68.4%) and 43 (75.4%) isolates exhibited an overexpression of MexAB-OprM and MexXY-OprM. Among burn isolates, 80% and 86.6% of them were mexB and mexY overexpressed, while 64.2% and 71.4% of ICU isolates exhibited mexB and mexY overexpression, correspondingly. The isolates were genotyped as 24 different RAPD profiles and were grouped into 15 clusters.

CONCLUSIONS

The data suggested that class 1 integron had a more significant role than efflux pumps in resistance to beta-lactams and aminoglycosides in burn and ICUs except for gentamicin in burn isolates. Based on our data, it is possible that efflux pumps were not the main cause of high-level resistance to antibiotics.

摘要

背景

外排泵的过度表达和 1 类整合子的存在是导致铜绿假单胞菌(尤其是烧伤和重症监护病房)对抗生素产生耐药性的最重要机制。本研究评估了 MexAB-OprM 和 MexXY-OprM 外排泵和 1 类整合子在烧伤和 ICU 分离株对铜绿假单胞菌抗生素耐药性中的作用。

方法

从伊朗西北部的四家医院获得 15 株烧伤和 42 株 ICU 分离株。通过纸片扩散和琼脂稀释法评估分离株的鉴定和抗生素耐药性。通过 PCR 和产物测序检测 1 类整合子及其相关耐药基因盒的存在。通过表型和基因(定量实时 PCR)方法评估外排泵的表达水平。通过随机扩增多态性 DNA 分型(RAPD-PCR)对分离株进行基因分型。

结果

所有烧伤分离株均为整合子阳性和多药耐药(MDR),而 78.5%和 69%的 ICU 分离株分别为 MDR 和整合子阳性。aadB 基因是最常见的基因盒(63.6%),其次是 aacA4(47.7%)。39(68.4%)和 43(75.4%)株表现出 MexAB-OprM 和 MexXY-OprM 的过度表达。在烧伤分离株中,80%和 86.6%的分离株 mexB 和 mexY 过度表达,而 64.2%和 71.4%的 ICU 分离株相应地表现出 mexB 和 mexY 过度表达。分离株被分为 24 种不同的 RAPD 图谱,并分为 15 个聚类。

结论

数据表明,除烧伤分离株中的庆大霉素外,1 类整合子在β-内酰胺类和氨基糖苷类抗生素耐药性方面比外排泵发挥更重要的作用。根据我们的数据,外排泵可能不是导致抗生素高水平耐药的主要原因。

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