Analysis of antibiotic susceptibility and genomic characteristics of Helicobacter pylori by whole-genome resequencing in Northern China

利用全基因组重测序技术分析中国北方幽门螺杆菌的抗生素敏感性和基因组特征

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Abstract

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.

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