Whole genome sequence analysis of Helicobacter pylori isolates reveals incomplete characterization of antimicrobial resistance mechanisms.

Helicobacter pylori, one of the most common causes of chronic bacterial infections worldwide and a carcinogen, has been associated with significant antimicrobial resistance. Here, whole genome sequencing and phenotypic susceptibility testing to amoxicillin, clarithromycin, levofloxacin, metronidazole, rifampin, and tetracycline of 530 H. pylori clinical isolates revealed significant genomic diversity not clustered by geographic location in the United States, and genome-wide association studies revealed incomplete genotypic characterization of antimicrobial resistance mechanisms for amoxicillin, metronidazole, and rifampin. Resistance to amoxicillin, metronidazole, and rifampin was not associated with a particular single-nucleotide polymorphism, the number of mutations in resistant versus susceptible isolates, or a particular mutation hotspot in a gene previously implicated in resistance. This study highlights a need for further elucidation of the genetic basis of antimicrobial resistance (beyond clarithromycin and levofloxacin) in this species.