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中国浙江分离出的48株幽门螺杆菌的全基因组测序分析及抗生素耐药情况

Whole-genome sequencing analyses and antibiotic resistance situation of 48 Helicobacter pylori strains isolated in Zhejiang, China.

作者信息

Fang Yunhui, Jiang Shiman, Zhou Xinxin, Zhou Wangxiao, Jiang Xinrong, Chen Lifeng, Wang Mengting, Chen Yunbo, Li Lanjuan

机构信息

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, National Medical Center for Infectious Diseases, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, 310003, China.

Jinan Microecological Biomedicine Shandong Laboratory, Jinan, Shandong, China.

出版信息

Gut Pathog. 2024 Oct 23;16(1):62. doi: 10.1186/s13099-024-00656-2.

Abstract

PURPOSE

In the Zhejiang region, research on Helicobacter pylori is lacking. The purpose of this study was to assess the extent of antibiotic resistance in H. pylori in this region, explore alternative methods for predicting the resistance patterns of H. pylori, and investigate the colonization of native gastric mucosa by other clades of H. pylori in the structure population of this bacterium.

METHODS

Strains were cultured under microaerobic conditions, and antimicrobial susceptibility testing (AST) was performed via agar dilution. Whole-genome sequencing (WGS) was performed via next-generation sequencing (NGS) technology. Epidemiological data including data from this study and reported articles from Zhejiang, China, were included. Further analyses based on AST, WGS, and epidemiological date include virulence genes, antibiotic resistance-related mutations, and phylogenetic trees based on 7 housekeeping genes and core-genome single nucleotide polymorphisms (SNPs).

RESULTS

The bacterial isolates in this study presented higher antibiotic resistance rates than previously reported, especially against levofloxacin and clarithromycin. The point mutation A2147G in 23 S rRNA is specific to clarithromycin resistance. Mutations at position/s 87 and/or 91 of the gyrA gene amino acid sequence are highly consistent with levofloxacin resistance highly. The point mutations C1707T in 23 S rRNA and E463K in the gyrB gene have not been previously documented in China. All the bacterial isolates belong to Asian branches in the structure population. The resistance rate to clarithromycin of isolates from hosts born after January 1, 1977 is statistically higher than that of hosts born before 1977.

CONCLUSION

Eradication therapy based on AST results is urgently needed in Zhejiang. The point mutation A2147G in 23 S rRNA and point mutations in the gyrA gene at amino acid/s 87 and/or 91 are sufficient for predicting resistance to clarithromycin and levofloxacin, respectively. The isolate with the mutation E463K in the gyrB gene represents a significant contribution to the field. Mutations in 23 S rRNA may offer valuable insights into the dynamics of H. pylori transmission among hosts.

摘要

目的

在浙江地区,幽门螺杆菌的研究较为缺乏。本研究的目的是评估该地区幽门螺杆菌的抗生素耐药程度,探索预测幽门螺杆菌耐药模式的替代方法,并研究该细菌结构群体中其他幽门螺杆菌进化枝在本地胃黏膜中的定植情况。

方法

菌株在微需氧条件下培养,并通过琼脂稀释法进行抗菌药物敏感性试验(AST)。通过下一代测序(NGS)技术进行全基因组测序(WGS)。纳入了包括本研究数据以及中国浙江报道文章的流行病学数据。基于AST、WGS和流行病学数据的进一步分析包括毒力基因、抗生素耐药相关突变以及基于7个管家基因和核心基因组单核苷酸多态性(SNP)的系统发育树。

结果

本研究中的细菌分离株呈现出比先前报道更高的抗生素耐药率,尤其是对左氧氟沙星和克拉霉素。23S rRNA中的点突变A2147G是克拉霉素耐药的特异性突变。gyrA基因氨基酸序列第87位和/或91位的突变与左氧氟沙星耐药高度一致。23S rRNA中的点突变C1707T和gyrB基因中的E463K在中国此前未见报道。所有细菌分离株在结构群体中均属于亚洲分支。1977年1月1日以后出生的宿主分离株对克拉霉素的耐药率在统计学上高于1977年以前出生的宿主。

结论

浙江迫切需要基于AST结果的根除治疗。23S rRNA中的点突变A2147G以及gyrA基因第87位和/或91位氨基酸的点突变分别足以预测对克拉霉素和左氧氟沙星的耐药性。gyrB基因中具有E463K突变的分离株对该领域有重大贡献。23S rRNA中的突变可能为幽门螺杆菌在宿主间传播的动态过程提供有价值的见解。

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