幽門螺桿菌抗生素耐藥基因的分子檢測及分子對接分析

發布時間：2021-06-23 15:10 原文鏈接：幽門螺桿菌抗生素耐藥基因的分子檢測及分子對接分析

Abstract 摘要

Aim:

To explore the mutation characteristics of H. pylori resistance-related genes to antibiotics of clarithromycin (CAM), levofloxacin (LVX) and metronidazole.

目的：

探討幽門螺桿菌對克拉霉素(CAM)、左氧氟沙星(LVX)和甲硝唑等抗生素耐藥相關基因的突變特點。

Methods:

23S rRNA, gyrA, gyrB, rdxA, and frxA genes were amplified and sequenced, respectively. Molecular docking study was performed to explore molecular interactions between chemotherapeutic agents and target proteins. What's more, we performed natural transformation with some of these mutated DNA fragments to see if they really impact susceptibility to antibiotics.

方法：

分別對23S rRNA、gyrA、gyrB、rdxA和frxA基因進行擴增和測序。使用分子對接探討抗生素藥物與靶蛋白之間的分子相互作用。更重要的是，本研究用其中一些突變的DNA片段進行了自然轉化實驗，看看它們是否真的會影響對抗生素的敏感性。

Results:

In the CAM-resistant strains, the mutation rate in site A2143G was 74.2% (n = 23). The interactions in sites of G1949A, C1953T, and G2211T with CAM were weaker after mutation. In the LVX-resistant strains, the mutation rates in 87 (N to K/I) and 91 (D to N/Y/G) of gyrA were 28.6% (n = 16) and 12.5% (n = 7), respectively. We could infer by docking studies that N87 K/I, D91Y/G/N, D99N, and D143E mutations in GyrA protein all had weakened interaction with LVX. The mutation types of RdxA protein consisted of protein truncation caused by premature stop codons (n = 26, 33.3%), frameshift mutations (n = 8, 10.3%), FMN-binding sites (n = 16, 20.5%), and the others (n = 11, 14.1%). Docking analysis showed that some mutations in those four types of RdxA protein could reduce interaction with MNZ, and play a significant role in antibiotic resistance.

結果：

在CAM耐藥菌株中，A2143G位點的突變率為74.2%（n=23）。G1949A、C1953T和G2211T的位點突變后與CAM的相互作用較弱。在LVX耐藥株中，gyrA的87（N～K/I）和91（D～N/Y/G）的突變率分別為28.6%（n＝16）和12.5%（n＝7）。我們通過分子對接研究推斷，GyrA蛋白的N87 K/I、D91Y/G/N、D99N和D143E突變都與LVX的相互作用減弱。RdxA蛋白的突變類型包括過早出現終止密碼子引起的蛋白截斷（n = 26，33.3%）、框移突變（n = 8，10.3%）、FMN結合位點（n = 16，20.5%）和其他（n = 11，14.1%）。分子對接分析表明，這4種類型的RdxA蛋白的一些突變可以減少與MNZ的相互作用，并在抗生素耐藥性中發揮重要作用。

Conclusion:

Our study suggested that in addition to the reported mutation sites, H. pylori antibiotic resistance in this region may also be associated with changes in some new sites. Our study provides novel ideas and methods for the identification of H. pylori resistancerelated mutations, and also clues and basis for further investigation on specific molecular mechanism.

結論：

我們的研究表明，除了已報道的突變位點外，幽門螺桿菌抗生素耐藥性還可能與一些新位點的變化有關。我們的研究為幽門螺桿菌耐藥相關突變的鑒定提供了新的思路和方法，也為進一步研究具體的分子機制提供了線索和依據。

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