| Accession | ARO:3003937 |
| CARD Short Name | Nmen_PBP2_BLA |
| Definition | Point mutation in Neisseria meningititis PBP2 (penA) decreases affinity between beta-lactam antibiotic molecule and PBP2, thereby conferring resistance to beta-lactam. |
| AMR Gene Family | Penicillin-binding protein mutations conferring resistance to beta-lactam antibiotics |
| Drug Class | cephalosporin, penicillin beta-lactam |
| Resistance Mechanism | antibiotic target alteration |
| Resistomes with Sequence Variants | Neisseria gonorrhoeaewgs, Neisseria meningitidisg+wgs |
| Classification | 12 ontology terms | Show + process or component of antibiotic biology or chemistry + antibiotic molecule + mechanism of antibiotic resistance + beta-lactam antibiotic + antibiotic target alteration [Resistance Mechanism] + mutation conferring antibiotic resistance + determinant of antibiotic resistance + cephalosporin [Drug Class] + third-generation cephalosporin + beta-lactam resistant penicillin-binding proteins + penicillin beta-lactam [Drug Class] + antibiotic resistant gene variant or mutant |
| Parent Term(s) | 3 ontology terms | Show + confers_resistance_to_antibiotic ceftriaxone [Antibiotic] + confers_resistance_to_antibiotic cefixime [Antibiotic] + Penicillin-binding protein mutations conferring resistance to beta-lactam antibiotics [AMR Gene Family] |
| Publications | Zapun A, et al. 2016. Antibiotics (Basel) 5(4): Resistance to β-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins. (PMID 27690121) Gong Z, et al. 2016. Antimicrob. Agents Chemother. 60(4):2043-51 Novel Genes Related to Ceftriaxone Resistance Found among Ceftriaxone-Resistant Neisseria gonorrhoeae Strains Selected In Vitro. (PMID 26787702) Powell AJ, et al. 2009. J Biol Chem 284(2): 1202-1212. Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. (PMID 18986991) Takahata S, et al. 2006. Antimicrob. Agents Chemother. 50(11):3638-45 Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. (PMID 16940068) Johnson SR, et al. 2014. Antimicrob. Agents Chemother. 58(11):6986-9 In Vitro selection of Neisseria gonorrhoeae mutants with elevated MIC values and increased resistance to cephalosporins. (PMID 25199775) Bharat A, et al. 2015. Antimicrob. Agents Chemother. 59(8):5003-6 Effect of Variants of Penicillin-Binding Protein 2 on Cephalosporin and Carbapenem Susceptibilities in Neisseria gonorrhoeae. (PMID 25987627) |
Prevalence of Neisseria meningititis PBP2 conferring resistance to beta-lactam among the sequenced genomes, plasmids, and whole-genome shotgun assemblies available at NCBI or IslandViewer for 414 important pathogens (see methodological details and complete list of analyzed pathogens). Values reflect percentage of genomes, plasmids, genome islands, or whole-genome shotgun assemblies that have at least one hit to the AMR detection model. Default view includes percentages calculated based on Perfect plus Strict RGI hits. Select the checkbox to view percentages based on only Perfect matches to AMR reference sequences curated in CARD (note: this excludes resistance via mutation as references in protein variant models are often wild-type, sensitive sequences).
| Species | NCBI Chromosome | NCBI Plasmid | NCBI WGS | NCBI GI | GRDI-AMR2 |
|---|---|---|---|---|---|
| Neisseria gonorrhoeae | 0% | 0% | 1.33% | 0% | 0% |
| Neisseria meningitidis | 3.82% | 0% | 22.46% | 0% | 0% |
Model Type: protein variant model
Model Definition: Protein Variant Models (PVM) perform a similar search as Protein Homolog Models (PHM), i.e. detect protein sequences based on their similarity to a curated reference sequence, but secondarily screen query sequences for curated sets of mutations to differentiate them from antibiotic susceptible wild-type alleles. PVMs are designed to detect AMR acquired via mutation of house-keeping genes or antibiotic targets, e.g. a mutated gyrase resistant to aminocoumarin antibiotics. PVMs include a protein reference sequence (often from antibiotic susceptible wild-type alleles), a curated bit-score cut-off, and mapped resistance variants. Mapped resistance variants may include any or all of single point mutations, insertions, or deletions curated from the scientific literature. A Strict RGI match has a BLASTP bit-score above the curated BLASTP cutoff value and contains at least one curated mutation from amongst the mapped resistance variants, while a Loose RGI match has a bit-score less than the curated BLASTP bit-score cut-off but still contains at least one curated mutation from amongst the mapped resistance variants.
Bit-score Cut-off (blastP): 1000
PubMed: mutation data hand curated from the scientific literature, evaluated as conferring resistance (R). CRyPTIC: mutation data acquired from the CRyPTIC catalog, evaluated as resistant (R), susceptible (S), or undetermined (U). ReSeqTB: mutation data acquired from the ReSeqTB catalog, evaluated as conferring resistance (Minimal, Moderate, High), not conferring resistance (None), or Indeterminate. WHO: mutation data acquired from the WHO 2023 catalog, evaluated as resistant (R), susceptible (S), or undetermined (U).| Mutation | Mutation type | PubMed |
|---|---|---|
| I312M | single resistance variant | PMID:16940068 |
| V316T | single resistance variant | PMID:16940068 |
| G482S | single resistance variant | PMID:18986991 |
| A501P | single resistance variant | PMID:25199775 |
| F504L | single resistance variant | PMID:26787702 |
| A510V | single resistance variant | PMID:25987627 |
| N512Y | single resistance variant | PMID:25987627 |
| G545S | single resistance variant | PMID:16940068 |
| Curator | Description | Most Recent Edit |
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