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幽门螺杆菌克拉霉素耐药的早期基因诊断。

Early genetic diagnosis of clarithromycin resistance in .

机构信息

Research Center for the Prevention and Treatment of Drug Resistant Microbial Infection, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China.

Department of Pathology, Wannan Medical College, Wuhu 241002, Anhui Province, China.

出版信息

World J Gastroenterol. 2021 Jun 28;27(24):3595-3608. doi: 10.3748/wjg.v27.i24.3595.

Abstract

BACKGROUND

The drug resistance rate of clinical () isolates has increased. However, the mechanism of drug resistance remains unclear. In this study, drug-resistant strains were isolated from different areas and different populations of Chinese for genomic analysis.

AIM

To investigate drug-resistant genes in and find the genes for the early diagnosis of clarithromycin resistance.

METHODS

Three drug-resistant strains were isolated from patients with gastritis in Bama County, China. Minimal inhibitory concentrations of clarithromycin, metronidazole, and levofloxacin were determined and complete genome sequencing was performed with annotation. and genes were found in these strains and then detected by reverse transcription polymerase chain reaction. The relationships between or and clarithromycin resistance were ascertained with gene mutant and drug-resistant strains. The homology of the strains with was assessed through complete genome detection and identification. Differences in genome sequences, gene quantity, and gene characteristics were detected amongst the three strains. Prediction and analysis of the function of drug-resistant genes indicated that the RNA expression of and increased in the three strains, which was the same in the artificially induced clarithromycin-resistant bacteria. After gene knockout, the drug sensitivity of the strains was assessed.

RESULTS

The strains showing a high degree of homology with , , and genes were found in these strains; the expression of the genes and was associated with clarithromycin resistance.

CONCLUSION

and mutations may be the earliest and most persistent response to clarithromycin resistance, and they may be the potential target genes for the diagnosis, prevention, and treatment of clarithromycin resistance.

摘要

背景

临床分离株的耐药率有所增加。然而,耐药机制尚不清楚。本研究从中国不同地区和不同人群中分离耐药株进行基因组分析。

目的

研究耐克拉霉素 株的耐药基因,寻找早期诊断克拉霉素耐药的基因。

方法

从中国巴马县胃炎患者中分离出 3 株耐药 株。测定克拉霉素、甲硝唑和左氧氟沙星的最小抑菌浓度,并进行完整的基因组测序和注释。在这些菌株中发现了 和 基因,并通过逆转录聚合酶链反应进行检测。通过基因突变体和耐药菌株确定 或 与克拉霉素耐药的关系。通过全基因组检测和鉴定评估与 的菌株同源性。检测和比较这 3 株菌的基因组序列、基因数量和基因特征的差异。耐药基因的功能预测和分析表明,3 株菌中 和 的 RNA 表达均增加,在人工诱导的克拉霉素耐药菌中也有相同的表达。基因敲除后,评估菌株的药敏性。

结果

在这些菌株中发现了与 、 和 基因高度同源的菌株;基因 和 的表达与克拉霉素耐药相关。

结论

和 突变可能是对克拉霉素耐药的最早和最持久的反应,可能是诊断、预防和治疗克拉霉素耐药的潜在靶基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/862f/8240046/9c445efd09b2/WJG-27-3595-g001.jpg

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