Journal of Microbiology, Immunology and Infection (Feb 2023)

Multiple amino acid substitutions in penicillin-binding protein-1A confer amoxicillin resistance in refractory Helicobacter pylori infection

  • Chia-Jung Kuo,
  • Jun-Nong Ke,
  • Tony Kuo,
  • Cheng-Yu Lin,
  • Sen-Yung Hsieh,
  • Ya-Fang Chiu,
  • Hui-Yu Wu,
  • Mei-Zi Huang,
  • Ngoc-Niem Bui,
  • Cheng-Hsun Chiu,
  • Cheng-Tang Chiu,
  • Chih-Ho Lai

Journal volume & issue
Vol. 56, no. 1
pp. 40 – 47

Abstract

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Background: Amoxicillin resistance in Helicobacter pylori is mainly associated with mutations in penicillin-binding protein-1A (PBP-1A). However, the specific amino acid substitutions in PBP-1A that confer amoxicillin resistance in H. pylori remain to be investigated. Objective: This study aimed to investigate the molecular mechanism underlying amoxicillin resistance in patients with refractory H. pylori infection. Methods: Esophagogastroduodenoscopy (EGD) was performed in patients with persistent H. pylori infection after at least two courses of H. pylori eradication therapy between January-2018 to March-2021. Refractory H. pylori was cultured from the gastric biopsy specimens. Antibiotic susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs). Sequence analysis of pbp-1A was performed for amoxicillin-resistant strains. Results: Thirty-nine successfully cultured isolates were classified as refractory H. pylori isolates, and seventeen isolates were resistant to amoxicillin (MIC > 0.125 mg/L). Sequence analysis of resistant strains showed multiple mutations in the C-terminal region of PBP-1A that conferred amoxicillin resistance in H. pylori. However, the number of PBP-1A mutations did not correlate with the high MICs of amoxicillin-resistant isolates. Notably, some amino acid substitutions were identified in all Taiwanese isolates with history of eradication failure but not in published amoxicillin-susceptible strains, suggesting that the mutations may play a role in conferring antibiotic resistance to these strains. Conclusions: Our results show that amoxicillin resistance in refractory H. pylori is highly correlated with numerous PBP-1A mutations that are strain specific. Continuous improvements in diagnostic tools, particularly molecular analysis approaches, can help to optimize current antimicrobial regimens.

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