Population structure of Helicobacter pylori and antibiotic resistance-associated variants in a high-risk area of gastric cancer
Abstract
ABSTRACT The increasing antibiotic resistance of Helicobacter pylori has had a serious impact on gastric cancer prevention. Our study aimed to profile the genomic characteristics and explore variants associated with resistance in H. pylori strains from a high-risk area of gastric cancer in China. We isolated 153 strains from a community-based cohort and assessed their susceptibility to six antibiotics by MIC Test Strip and genomic characteristics by whole-genome sequencing. Phylogenetic analysis identified the strains as an independent cluster within H. pylori East Asian population (hpEastAsia). HefA, an efflux pump gene, showed the highest differentiation in the Linqu strains compared with the other Chinese strains. Bacterial genome-wide association study (GWAS) identified 86 resistance variants covering 44 genes. Novel resistance variants were found in lon and babA for metronidazole, HP1168 for clarithromycin, hcpC for levofloxacin, and sabA for rifamycin. Two newly identified hefA mutations (R229K and A283V) showed significant associations with metronidazole (P = 0.012) and tetracycline (P = 0.044) resistance, respectively. HefA mutations and GWAS variants were integrated with the significant literature-reported mutations to optimize the prediction models for metronidazole, levofloxacin, clarithromycin, and tetracycline resistance with area under the receiver operating characteristic curves of 0.82–0.93. Double-antibiotic resistance models were established for clinical…
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Evidence Hub reads this as a cohort study. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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