Identification of genetic determinants of antibiotic resistance in Helicobacter pylori isolates in Vietnam by high-throughput sequencing
Bibliographic record
Abstract
The aim of this study was to identify genetic factors responsible for antibiotic resistance in Helicobacter pylori, a bacterium that can cause long-term gastroduodenal disease. The primary resistance of H. pylori to commonly used antibiotics was studied, and high-throughput next-generation sequencing (NGS) was employed to discover genetic determinants of resistance using a reference-based approach. A total of 123 H. pylori strains were cultured and tested for antibiotic susceptibility using an E test. Genotypic analysis was performed using NGS data with ARIBA v2.14.7 and PlasmidSeeker v1.3 for plasmid detection. Statistical correlations between resistant genotypes and phenotypes were evaluated. In addition, a genome-wide association study (GWAS) and linear mixed model were used to identify genetic variants associated with antimicrobial resistance phenotypes while adjusting for covariates such as population structure. Our results showed that 78.2% of the strains were resistant to metronidazole (MTZ), 22.5% to levofloxacin (LVX), 43.5% to clarithromycin (CLR) and 13.7% to amoxicillin (AMX). Resistance to tetracycline was not detected. Multi-drug resistance was detected in 48.8% of the strains. While plasmids were not detected, chromosomal genetic determinants of resistance to CLR, LVX, and AMX were identified, including mutations in 23S rRNA (A2142G and A2143G), gyrA (N87K/Y and D91Y/N/G), and pbp1 A (F366L, S414R, F473V, G595_V596insE, as well as the mutations T558S and T593A/G/P/S). Additionally, missense, frameshift, and nonsense mutations in rdxA were identified as genetic determinants of resistance to MTZ. No genetic determinants associated with tetracycline resistance were detected. A strong correlation was observed between resistance genotypes and phenotypes for CLR, LVX, AMX, and MTZ. In addition, we found that missense, frameshift and nonsense mutations in rdxA were genetic determinants of resistance to MTZ. We did not detect any genetic determinants associated with tetracycline resistance. There was a strong correlation between resistance genotypes and phenotypes for CLR, LVX, AMX, and MTZ. Furthermore, unitig-based GWAS revealed that AMX, LVX, and CLR resistance in H. pylori was mainly caused by chromosomal mutations that affected the targets of these antibiotics (pbp1 A, gyrA, and 23S rRNA, respectively). Our results highlight the need for regular evaluation and alternative therapies in Vietnam, given the high rates of H. pylori resistance to CLR, MTZ, and LVX. Our study also demonstrated the high capacity of NGS to detect genetic resistance determinants and its potential for implementation in local treatment policies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".