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

• Main Authors: Ng, Heng Kang, Chua, Kek Heng, Kee, Boon Pin, Chuah, Kee Huat, Por, Lip Yee, Puah, Suat Moi
• Format: Article
• Published: Microbiology Society 2024
• Subjects: QA75 Electronic computers. Computer science; R Medicine (General)
• Online Access: http://eprints.um.edu.my/45885/; https://doi.org/10.1099/jmm.0.001832

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.