中国北方地区幽门螺杆菌抗生素敏感性及全基因组重测序的基因组特征分析
Analysis of antibiotic susceptibility and genomic characteristics of Helicobacter pylori by whole-genome resequencing in Northern China.
作者信息
Wang Yaxuan, Jiang Tiantong, Liu Xiaochuan, Sa Rina, Zhu Xiaoyan, Hu Jihong
机构信息
National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing, P.R. China.
Department of Gastroenterology, Guang' anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
出版信息
Braz J Microbiol. 2025 Mar;56(1):487-498. doi: 10.1007/s42770-024-01582-w. Epub 2024 Dec 11.
INTRODUCTION
Helicobacter pylori (H. pylori) is a major human pathogen whose increased antibiotic resistance poses a serious threat to human health.
AIM
The aim of this study is to further explore the association between H. pylori resistance to clarithromycin, levofloxacin, metronidazole, amoxicillin, rifampicin, tetracycline and its genomic characteristics.
METHODOLOGY
Using H. pylori isolates, we studied their susceptibility to six antibiotics by the agar dilution method. By performing whole-genome resequencing of the H. pylori genomic DNA, the differences in single nucleotide polymorphisms (SNPs) between phenotype resistant and sensitive strains were statistically analyzed to identify potential mutation sites related to drug resistance, and the consistency between genotype and phenotype resistance was analyzed.
RESULTS
The drug resistance rates of 65 H. pylori isolates are as follows: clarithromycin 36.9%, levofloxacin 29.2%, metronidazole 63.1%, amoxicillin 7.7%, rifampicin 12.3%, and tetracycline 3.1%. Based on the whole genome resequencing results of H. pylori isolates, 10 new mutations that may be related to drug resistance were identified. There is strong consistency between the genotype and phenotype resistance of clarithromycin and levofloxacin.
CONCLUSION
The resistance rate to amoxicillin and tetracycline is relatively low in Northern China. and the above two antibiotics can be given priority for clinical treatment. It has a high resistance rate to metronidazole and should be avoided as much as possible, or combined with other drugs for treatment. The 10 mutations identified through analysis that only exist in drug-resistant strains may be associated with levofloxacin, metronidazole, amoxicillin, and rifampicin resistance, respectively. The results indicate that genotype testing of H. pylori can serve as a method for predicting its resistance to clarithromycin and levofloxacin.
引言
幽门螺杆菌（H. pylori）是一种主要的人类病原体，其抗生素耐药性增加对人类健康构成严重威胁。
目的
本研究旨在进一步探讨幽门螺杆菌对克拉霉素、左氧氟沙星、甲硝唑、阿莫西林、利福平、四环素的耐药性与其基因组特征之间的关联。
方法
使用幽门螺杆菌分离株，通过琼脂稀释法研究其对六种抗生素的敏感性。通过对幽门螺杆菌基因组DNA进行全基因组重测序，对表型耐药菌株和敏感菌株之间的单核苷酸多态性（SNP）差异进行统计分析，以鉴定与耐药性相关的潜在突变位点，并分析基因型与表型耐药性之间的一致性。
结果
65株幽门螺杆菌分离株的耐药率如下：克拉霉素36.9%，左氧氟沙星29.2%，甲硝唑63.1%，阿莫西林7.7%，利福平12.3%，四环素3.1%。基于幽门螺杆菌分离株的全基因组重测序结果，鉴定出10个可能与耐药性相关的新突变。克拉霉素和左氧氟沙星的基因型与表型耐药性之间具有很强的一致性。
结论
中国北方地区对阿莫西林和四环素的耐药率相对较低，临床治疗可优先选用上述两种抗生素。对甲硝唑耐药率高，应尽量避免使用，或与其他药物联合使用。通过分析鉴定出的仅存在于耐药菌株中的10个突变可能分别与左氧氟沙星、甲硝唑、阿莫西林和利福平耐药性相关。结果表明，幽门螺杆菌基因型检测可作为预测其对克拉霉素和左氧氟沙星耐药性的一种方法。
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