ArticlemBio2022
Integrative Reverse Genetic Analysis Identifies Polymorphisms Contributing to Decreased Antimicrobial Agent Susceptibility in
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Clinical and Epidemiological Landscape of Antimicrobial Resistance and Virulence inAntibiotics (Basel, Switzerland) · 2026Review
- Identification ofAntimicrobial agents and chemotherapy · 2026Article
- Virulence modulation and biofilm inhibition of Streptococcus pyogenes by metabolites from endophytic fungi associated with Vanda tessellata.Molecular biology reports · 2026Article
- Genomic and patient epidemiology ofMicrobiology spectrum · 2026Article
- The WHO priority list of antibiotic-resistant bacteria: challenges and opportunities for next-generation antimicrobial development.Frontiers in pharmacology · 2026Review
- Elucidating the role of group A Streptococcus genomics and pharyngeal microbiota in acute paediatric pharyngitis.Scientific reports · 2025Article
- Molecular Characterization ofMicroorganisms · 2025Article
- ICESp1109, a Novel Hybrid Integrative Conjugative Element of Macrolide-Resistant Streptococcus pyogenes Serotype M77 Collected Between 2003 and 2017 in Poland.The Journal of infectious diseases · 2025Article
- Exploring risk factors, etiology, and clinical outcomes of acute bacterial meningitis in children under 7 years in Oman.Journal of education and health promotion · 2025Article
- Invasive group A Streptococcus infection (Streptococcus pyogenes): Current situation in Spain.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2024Article
- Article
- Post-Meningitic Syndrome: Pathophysiology and Consequences of Streptococcal Infections on the Central Nervous System.International journal of molecular sciences · 2024Review
- Review
- A Review of the Impact of Streptococcal Infections and Antimicrobial Resistance on Human Health.Antibiotics (Basel, Switzerland) · 2024Review
- Inter-species gene flow drives ongoing evolution of Streptococcus pyogenes and Streptococcus dysgalactiae subsp. equisimilis.Nature communications · 2024Article
- Comparative molecular docking and toxicity between carbon-capped metal oxide nanoparticles and standard drugs in cancer and bacterial infections.BioImpacts : BI · 2024Article
- A New Integrative and Mobilizable Element Is a Major Contributor to Tetracycline Resistance inAntibiotics (Basel, Switzerland) · 2023Article
- A review of penicillin binding protein and group AFrontiers in cellular and infection microbiology · 2023Review
- Genome-Wide Transposon Mutagenesis Screens Identify Group A Streptococcus Genes Affecting Susceptibility to β-Lactam Antibiotics.Journal of bacteriology · 2022Article
- Host-dependent resistance of Group A Streptococcus to sulfamethoxazole mediated by a horizontally-acquired reduced folate transporter.Nature communications · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identification of genetic polymorphisms causing increased antibiotic resistance in bacterial pathogens traditionally has proceeded from observed phenotype to defined mutant genotype. The availability of large collections of microbial genome sequences that lack antibiotic susceptibility metadata provides an important resource and opportunity to obtain new information about increased antimicrobial resistance by a reverse genotype-to-phenotype bioinformatic and experimental workflow. We analyzed 26,465 genome sequences of Streptococcus pyogenes, a human pathogen causing 700 million infections annually. The population genomic data identified amino acid changes in penicillin-binding proteins 1A, 1B, 2A, and 2X with signatures of evolution under positive selection as potential candidates for causing decreased susceptibility to β-lactam antibiotics. Construction and analysis of isogenic mutant strains containing individual amino acid replacements in penicillin-binding protein 2X (PBP2X) confirmed that the identified residues produced decreased susceptibility to penicillin. We also discovered the first chimeric PBP2X in S. pyogenes and show that strains containing it have significantly decreased β-lactam susceptibility. The novel integrative reverse genotype-to-phenotype strategy presented is broadly applicable to other pathogens and likely will lead to new knowledge about antimicrobial agent resistance, a massive public health problem worldwide.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.