ArticlePLoS pathogens2022
The acquisition of clinically relevant amoxicillin resistance in Streptococcus pneumoniae requires ordered horizontal gene transfer of four loci.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Antibacterial Benzimidazole-2-Methanamines as Allosteric Modulators ofJournal of medicinal chemistry · 2026Article
- A mini review of genome-predicted β-lactam susceptibility inFrontiers in cellular and infection microbiology · 2026Review
- Lineage structure and penicillin-binding protein variability in clinicalFrontiers in public health · 2026Article
- The effect of MurM and a branched cell wall structure on penicillin resistance inJournal of bacteriology · 2025Article
- Machine learning-based virtual screening and density functional theory characterisation of natural inhibitors targeting mutant PBP2x in Streptococcus pneumoniae.Scientific reports · 2025Article
- Review
- Amoxicillin-non-susceptibleAntimicrobial agents and chemotherapy · 2025Observational
- The Role of Livestock Antibiotic Use in Microbiota Dysbiosis and Neuroinflammation.Antibiotics (Basel, Switzerland) · 2025Review
- Make-or-break prime editing for genome engineering in Streptococcus pneumoniae.Nature communications · 2025Article
- PneumoBrowse 2: an integrated visual platform for curated genome annotation and multiomics data analysis of Streptococcus pneumoniae.Nucleic acids research · 2025Article
- Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance.The Journal of infectious diseases · 2024Article
- Non-Canonical Aspects of Antibiotics and Antibiotic Resistance.Antibiotics (Basel, Switzerland) · 2024Review
- Coordinated regulation of osmotic imbalance by c-di-AMP shapes ß-lactam tolerance in Group BmicroLife · 2024Article
- Genome-wide transformation reveals extensive exchange across closely related Bacillus species.Nucleic acids research · 2023Article
- Loss of Pde1 function acts as an evolutionary gateway to penicillin resistance inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Zinc Oxide Quantum Dots May Provide a Novel Potential Treatment for Antibiotic-ResistantMolecules (Basel, Switzerland) · 2023Article
- Amoxicillin-resistanteLife · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding how antimicrobial resistance spreads is critical for optimal application of new treatments. In the naturally competent human pathogen Streptococcus pneumoniae, resistance to β-lactam antibiotics is mediated by recombination events in genes encoding the target proteins, resulting in reduced drug binding affinity. However, for the front-line antibiotic amoxicillin, the exact mechanism of resistance still needs to be elucidated. Through successive rounds of transformation with genomic DNA from a clinically resistant isolate, we followed amoxicillin resistance development. Using whole genome sequencing, we showed that multiple recombination events occurred at different loci during one round of transformation. We found examples of non-contiguous recombination, and demonstrated that this could occur either through multiple D-loop formation from one donor DNA molecule, or by the integration of multiple DNA fragments. We also show that the final minimum inhibitory concentration (MIC) differs depending on recipient genome, explained by differences in the extent of recombination at key loci. Finally, through back transformations of mutant alleles and fluorescently labelled penicillin (bocillin-FL) binding assays, we confirm that pbp1a, pbp2b, pbp2x, and murM are the main resistance determinants for amoxicillin resistance, and that the order of allele uptake is important for successful resistance evolution. We conclude that recombination events are complex, and that this complexity contributes to the highly diverse genotypes of amoxicillin-resistant pneumococcal isolates.
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