Mutations Related to Antibiotics Resistance in Helicobacter pylori Clinical Isolates from Bangladesh

Abstract

Current management of gastric inflammation involves the eradication of Helicobacter pylori. However, the effectiveness of commonly used antibiotics against H. pylori infection has decreased due to antibiotic resistance. Phenotypic-based diagnostics are laborious and finding the cause of resistance can be difficult. Therefore, early detection and understanding of the underlying mechanism of this resistance are necessary. This study evaluated the mutations in the genes related to the Antimicrobial Resistance (AMR) of the clinical isolates from Bangladeshi subjects. Whole-genome sequencing was performed on 56 isolates and the genes (such as pbp1a, rdxA, ribF, fur, gyrA, gyrB, 23S rRNA, and infB) were extracted. The reads were assembled, and the SNPs were extracted by the latest pipeline for antibiotic mutation analysis, ARIBA. The mutations and the association with the antibiotic phenotypes were evaluated using Fisher’s exact test. In this study, the clarithromycin resistance rate was high, 39.3% (22/56), with the median MIC 24 mg/L ranging from 2 to 128 mg/L. The mutation of A2147G was significantly associated with resistance (p = 0.000018) but not in locus A2146G (p = 0.056). Levofloxacin also posed a high resistance. We observed that the mutation of D91N (but not D91Y) (p = 0.002) and N87K (p = 0.002) of gyrA was associated with levofloxacin resistance. Mutations in locus A343V (p = 0.041) of gyrB also showed a significant association. Meanwhile, in the pbp1a gene, several mutations might explain the resistance; they were G594fs (p = 0.036), K306R (p = 0.036), N562Y (p = 0.0006), and V45I (p = 0.018). The prevalence of metronidazole was exceptionally high (96.4%), and numerous mutations occurred in rdxA genes, including the truncation of genes. These results imply that the mutation in genes encoding the target protein of antibiotics remains the critical resistance mechanism in H. pylori.

Antibiotic resistance and heteroresistance in Helicobacter pylori isolates from symptomatic Vietnamese children: A prospective multicenter study

“…18 In Hanoi (Northern Vietnam), the CLA resistance rate was extremely high at 96.7% in children with peptic ulcers, regardless of the pretreatment history. 37 However, our CLA resistance rate is approximately 2.5-3.5 times higher than reported for America (19%; 95% CI:13-26), Europe (24%; 95% CI: 19-30), and Southeast Asia (29%; 95% CI: [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38], but similar to that in the Western Pacific region (85%; 95% CI: 80-90). 6 This may be related to CLA exposure during childhood, including the treatment of respiratory infections, self-medication with antibiotics, 31 over-the-counter purchase, and inadequate adherence to treatment regimens as CLA is an antibiotic in the first-line therapy for H. pylori.…”

“…Additionally, several point mutations in the 23 s rRNA gene of H. pylori are associated with CLA resistance 38–40 . Through Sanger sequencing, we identified a high rate (98.4%) of a unique mutation at the A2143G nucleotide position.…”

“…Additionally, several point mutations in the 23 s rRNA gene of H. pylori are associated with CLA resistance. [38][39][40] TA B L E 1 Characteristics of the H. pylori-infected patients with and without antimicrobial susceptibility testing results.…”

Identification, Genome Sequencing, and Characterizations of Helicobacter pylori Sourced from Pakistan

“…sively reported virulent and drug-resistant strains of H. pylori from Bangladesh, Ind China [21,22]. However, to the best of our knowledge, no comprehensive genom studies have been reported of H. pylori from Pakistan.…”

“…H. pylori incidence is considerably high in South Asian populations. Such genome-based studies have compressively reported virulent and drug-resistant strains of H. pylori from Bangladesh, India, and China [21,22]. However, to the best of our knowledge, no comprehensive genome-based studies have been reported of H. pylori from Pakistan.…”