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Next-Generation Sequencing of the Whole Bacterial Genome for Tracking Molecular Insight into the Broad-Spectrum Antimicrobial Resistance of Helicobacter pylori Clinical Isolates from the Democratic Republic of Congo

202055 citationsOpen accessUniversité de Kinshasa (UNIKIN)

In plain language

Conventional antimicrobial susceptibility testing for Helicobacter pylori is laborious and largely unavailable in African settings. Whole genome sequencing was evaluated as an alternative tool for predicting antimicrobial resistance using 102 clinical isolates collected from the Democratic Republic of Congo. Phenotypic testing revealed broad-spectrum resistance across the isolates, with resistance frequencies ranging from 23.5 to 90.0 per cent. Genomic analysis achieved a 100 per cent variant discovery rate in resistance-related genes, uncovering established mutations alongside several new putative resistance genotypes in genes such as pbp1A, gyrA, gyrB, and rdxA. The sequencing-based method demonstrated high predictive accuracy for phenotypic resistance, particularly against amoxicillin, clarithromycin, and levofloxacin, achieving agreement scores above 0.80. The findings confirm that bacterial genome sequencing provides an accurate alternative to phenotypic testing for guiding treatment choices and public health policies.

Key takeaways

  • Helicobacter pylori isolates from the Democratic Republic of Congo show broad-spectrum antimicrobial resistance rates ranging from 23.5 to 90.0 per cent.
  • Whole genome sequencing achieved a 100 per cent variant discovery rate and revealed multiple novel putative resistance genotypes.
  • Genomic sequencing accurately predicts phenotypic resistance to amoxicillin, clarithromycin, and levofloxacin with agreement metrics exceeding 0.80.
  • Whole genome sequencing offers a dependable alternative to conventional susceptibility testing for informing clinical and public health choices.

Why it matters

Standard laboratory testing to guide treatment for Helicobacter pylori infections is difficult to access in many African regions. Validating whole genome sequencing as a dependable predictor of drug resistance allows healthcare providers to identify effective antibiotics more reliably. This helps overcome diagnostic hurdles, reduces treatment failures, and assists public health authorities in monitoring and tackling the spread of drug-resistant bacteria.

Commercialisation angle

The findings could enable the development of genomic diagnostic services and decision-support software for clinical laboratories, healthcare providers, and public health agencies. Based on the abstract, the sequencing and variant-prediction method is applied and tested on clinical isolates in a research environment, but it has not yet been packaged into a standardised commercial diagnostic product or deployed clinical service.

AI-generated from the published abstract. Always read the original work before citing.

Abstract

Antimicrobial susceptibility testing (AST) is increasingly needed to guide the <i>Helicobacter</i> <i>pylori</i> (<i>H. pylori</i>) treatment but remains laborious and unavailable in most African countries. To assess the clinical relevance of bacterial whole genome sequencing (WGS)-based methods for predicting drug susceptibility in African <i>H. pylori</i>, 102 strains isolated from the Democratic Republic of Congo were subjected to the phenotypic AST and next-generation sequencing (NGS). WGS was used to screen for the occurrence of genotypes encoding antimicrobial resistance (AMR). We noted the broad-spectrum AMR of <i>H. pylori</i> (rates from 23.5 to 90.0%). A WGS-based method validated for variant discovery in AMR-related genes (discovery rates of 100%) helped in identifying mutations of key genes statistically related to the phenotypic AMR. These included mutations often reported in Western and Asian populations and, interestingly, several putative AMR-related new genotypes in the <i>pbp1A</i> (e.g., T558S, F366L), <i>gyrA</i> (e.g., A92T, A129T), <i>gyrB</i> (e.g., R579C), and <i>rdxA</i> (e.g., R131_K166del) genes. WGS showed high performance for predicting AST phenotypes, especially for amoxicillin, clarithromycin, and levofloxacin (Youden's index and Cohen's Kappa > 0.80). Therefore, WGS is an accurate alternative to the phenotypic AST that provides substantial decision-making information for public health policy makers and clinicians in Africa, while providing insight into AMR mechanisms for researchers.

Research topics

  • Helicobacter pylori-related gastroenterology studies
  • Veterinary medicine and infectious diseases
  • Mycobacterium research and diagnosis

Read the original research

This page summarises published work. The authoritative version sits with the publisher.

DOI: 10.3390/microorganisms8060887

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