阿莫西林
幽门螺杆菌
微生物学
青霉素结合蛋白
生物
青霉素
抗生素耐药性
抗生素
遗传学
作者
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
标识
DOI:10.1016/j.jmii.2022.07.006
摘要
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.This study aimed to investigate the molecular mechanism underlying amoxicillin resistance in patients with refractory H. pylori infection.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.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.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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