ArticlePLoS genetics2014
Comprehensive identification of single nucleotide polymorphisms associated with beta-lactam resistance within pneumococcal mosaic genes.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
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Who cites it
130 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- Genome shuffling enables quantitative trait locus mapping in Bacillus subtilis.Nature communications · 2026Article
- ALPAR: automated learning pipeline for antimicrobial resistance.Bioinformatics (Oxford, England) · 2026Article
- Epistasis and co-adaptation in bacterial genome evolution.Nature reviews. Genetics · 2026Review
- GeneScanner: profiling genetic variation across bacterial populations.Microbial genomics · 2026Article
- A versatile multi-components mixed model for bacterial-Genome Wide association studies.Nature communications · 2026Article
- BaGPipe: an automated, reproducible, and flexible pipeline for bacterial genome-wide association studies.BMC microbiology · 2026Article
- Article
- Advancing microbial risk assessment: perspectives from the evolution of detection technologies.NPJ science of food · 2025Review
- Bacterial genome-wide association studies: exploring the genetic variation underlying bacterial phenotypes.Applied and environmental microbiology · 2025Review
- Identification of genetic determinants of antibiotic resistance in Helicobacter pylori isolates in Vietnam by high-throughput sequencing.BMC microbiology · 2025Article
- Influence of Sequencing Technology on Pangenome-Level Analysis and Detection of Antimicrobial Resistance Genes in ESKAPE Pathogens.Open forum infectious diseases · 2025Article
- Predicting antimicrobial resistance inComputational and structural biotechnology journal · 2024Article
- Article
- Population genomics of Streptococcus mitis in UK and Ireland bloodstream infection and infective endocarditis cases.Nature communications · 2024Article
- Optimising machine learning prediction of minimum inhibitory concentrations inMicrobial genomics · 2024Article
- Convergent impact of vaccination and antibiotic pressures on pneumococcal populations.Cell chemical biology · 2024Review
- Nosocomial surveillance of multidrug-resistantMicrobiology spectrum · 2024Article
- Streptococcus suis serotype 9 in Italy: genomic insights into high-risk clones with emerging resistance to penicillin.The Journal of antimicrobial chemotherapy · 2024Article
- Integrating Genomic Data with the Development of CRISPR-Based Point-of-Care-Testing for Bacterial Infections.Current clinical microbiology reports · 2024Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors.
Funding
Abstract
Traditional genetic association studies are very difficult in bacteria, as the generally limited recombination leads to large linked haplotype blocks, confounding the identification of causative variants. Beta-lactam antibiotic resistance in Streptococcus pneumoniae arises readily as the bacteria can quickly incorporate DNA fragments encompassing variants that make the transformed strains resistant. However, the causative mutations themselves are embedded within larger recombined blocks, and previous studies have only analysed a limited number of isolates, leading to the description of "mosaic genes" as being responsible for resistance. By comparing a large number of genomes of beta-lactam susceptible and non-susceptible strains, the high frequency of recombination should break up these haplotype blocks and allow the use of genetic association approaches to identify individual causative variants. Here, we performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) and indels that could confer beta-lactam non-susceptibility using 3,085 Thai and 616 USA pneumococcal isolates as independent datasets for the variant discovery. The large sample sizes allowed us to narrow the source of beta-lactam non-susceptibility from long recombinant fragments down to much smaller loci comprised of discrete or linked SNPs. While some loci appear to be universal resistance determinants, contributing equally to non-susceptibility for at least two classes of beta-lactam antibiotics, some play a larger role in resistance to particular antibiotics. All of the identified loci have a highly non-uniform distribution in the populations. They are enriched not only in vaccine-targeted, but also non-vaccine-targeted lineages, which may raise clinical concerns. Identification of single nucleotide polymorphisms underlying resistance will be essential for future use of genome sequencing to predict antibiotic sensitivity in clinical microbiology.
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