Genetic variations of penicillin- binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia

Ng, Heng Kang and Chua, Kek Heng and Kee, Boon Pin and Chuah, Kee Huat and Por, Lip Yee and Puah, Suat Moi (2024) Genetic variations of penicillin- binding protein 1A: insights into the current status of amoxicillin-based regimens for Helicobacter pylori eradication in Malaysia. Journal of Medical Microbiology, 73 (5). 001832. ISSN 0022-2615, DOI https://doi.org/10.1099/jmm.0.001832.

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Official URL: https://doi.org/10.1099/jmm.0.001832

Abstract

Introduction. Resistance towards amoxicillin in Helicobacter pylori causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard H. pylori treatment regimen includes a 14 - day course of high - dose proton - pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy. Hypothesis/Gap Statement. The high eradication rate with amoxicillin- based treatment could be attributed to the primary resistance rates of amoxicillin being relatively low at 0%, however, a low rate of secondary resistance has been documented in Malaysia recently. Aim. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of H. pylori , correlating with amoxicillin resistance in the Malaysian population. Methodology. The full-length pbp1A gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of H. pylori - positive treatment - na & iuml;ve Malaysian patients. The sequences were then compared with reference H. pylori strain ATCC 26695 for mutation and variant detection. A phylogenetic analysis of 50 sequences along with 43 additional sequences from the NCBI database was performed. These additional sequences included both amoxicillin- resistant strains ( n =20) and amoxicillin- sensitive strains ( n =23). Results. There was a total of 21 variants of amino acids, with three of them located in or near the PBP- motif (SKN402- 404). The percentages of these three variants are as follows: K403X, 2%; S405I, 2% and E406K, 16%. Based on the genetic markers identified, the resistance rate for amoxicillin in our sample remained at 0%. The phylogenetic examination suggested that H. pylori might exhibit unique conserved pbp1A sequences within the Malaysian context. Conclusions. Overall, the molecular analysis of PBP1A supported the therapeutic superiority of amoxicillin- based regimens. Therefore, it is crucial to continue monitoring the amoxicillin resistance background of H. pylori with a larger sample size to ensure the sustained effectiveness of amoxicillin- based treatments in Malaysia.

Item Type: Article
Funders: Universiti Malaya (IIRG029A/B/C-2019)
Uncontrolled Keywords: amoxicillin resistance; full- length sequencing; Helicobacter pylori; PBP1A; phylogenetic analysis
Subjects: Q Science > QA Mathematics > QA75 Electronic computers. Computer science
R Medicine > R Medicine (General)
Divisions: Faculty of Computer Science & Information Technology > Department of Computer System & Technology
Faculty of Medicine > Biomedical Science Department
Faculty of Medicine > Medicine Department
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 13 Nov 2024 09:06
Last Modified: 13 Nov 2024 09:06
URI: http://eprints.um.edu.my/id/eprint/45885

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