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 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

Affiliations

Chia-Jung Kuo: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Jun-Nong Ke: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Tony Kuo: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Cheng-Yu Lin: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Sen-Yung Hsieh: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Ya-Fang Chiu: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Microbiology and Immunology, Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan
Hui-Yu Wu: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Mei-Zi Huang: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Ngoc-Niem Bui: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Faculty of Medicine, Can Tho University of Medicine and Pharmacy, Can Tho, Viet Nam
Cheng-Hsun Chiu: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
Cheng-Tang Chiu: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
Chih-Ho Lai: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Microbiology and Immunology, Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan; Department of Medical Research, School of Medicine, China Medical University and Hospital, Taichung, Taiwan; Department of Nursing, Asia University, Taichung, Taiwan; Corresponding author. Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

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.

Published in Journal of Microbiology, Immunology and Infection

ISSN: 1684-1182 (Print)
Publisher: Elsevier
Country of publisher: Hong Kong
LCC subjects: Science: Microbiology
Website: https://www.sciencedirect.com/journal/journal-of-microbiology-immunology-and-infection

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