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

Resistance towards amoxicillin in causes significant therapeutic impasse in healthcare settings worldwide. In Malaysia, the standard treatment regimen includes a 14-day course of high-dose proton-pump inhibitor (rabeprazole, 20 mg) with amoxicillin (1000 mg) dual therapy. 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. This study aims to investigate the amino acid mutations and related genetic variants in PBP1A of , correlating with amoxicillin resistance in the Malaysian population. The full-length gene was amplified via PCR from 50 genomic DNA extracted from gastric biopsy samples of -positive treatment-naïve Malaysian patients. The sequences were then compared with reference 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 ( =20) and amoxicillin-sensitive strains ( =23). 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 might exhibit unique conserved sequences within the Malaysian context. 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 with a larger sample size to ensure the sustained effectiveness of amoxicillin-based treatments in Malaysia.