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Updated: Aug 31, 2025
Gastric Mucosa Quantitative Polymerase Chain Reaction Analysis for Detecting Helicobacter pylori and Antibiotic Resistance
Published on: March 7, 2025
Multiple amino acid substitutions in penicillin-binding protein-1A confer amoxicillin resistance in refractory
Chia-Jung Kuo1, Jun-Nong Ke2, Tony Kuo1
1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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.
Insights
Amoxicillin resistance in Helicobacter pylori is linked to mutations in penicillin-binding protein-1A (PBP-1A). Identifying these specific PBP-1A mutations can guide better treatment strategies for resistant infections.
Area of Science:
- Microbiology
- Genetics
- Pharmacology
Background:
- Amoxicillin resistance in Helicobacter pylori is primarily linked to mutations in penicillin-binding protein-1A (PBP-1A).
- Specific amino acid substitutions in PBP-1A conferring amoxicillin resistance in H. pylori require further investigation.
Purpose of the Study:
- To investigate the molecular mechanisms of amoxicillin resistance in patients with refractory H. pylori infections.
- To identify specific PBP-1A mutations associated with amoxicillin resistance in H. pylori.
Main Methods:
- Esophagogastroduodenoscopy (EGD) and gastric biopsy for H. pylori culture from patients with treatment-refractory infections.
- Antibiotic susceptibility testing to determine minimum inhibitory concentrations (MICs) for amoxicillin.
- Sequence analysis of the pbp-1A gene in amoxicillin-resistant H. pylori isolates.
Main Results:
- Seventeen of thirty-nine refractory H. pylori isolates exhibited amoxicillin resistance (MIC > 0.125 mg/L).
- Sequence analysis revealed multiple PBP-1A mutations in the C-terminal region of resistant strains, correlating with amoxicillin resistance.
- Specific amino acid substitutions in PBP-1A were identified in Taiwanese isolates with eradication failure, suggesting a role in resistance.
Conclusions:
- Amoxicillin resistance in refractory H. pylori is strongly associated with specific, strain-dependent PBP-1A mutations.
- Molecular analysis of PBP-1A mutations can aid in optimizing antimicrobial treatment regimens for H. pylori infections.
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