Neisseria meningititis PBP2 conferring resistance to beta-lactam

Accession ARO:3003937
CARD Short NameNmen_PBP2_BLA
DefinitionPoint mutation in Neisseria meningititis PBP2 (penA) decreases affinity between beta-lactam antibiotic molecule and PBP2, thereby conferring resistance to beta-lactam.
AMR Gene FamilyPenicillin-binding protein mutations conferring resistance to beta-lactam antibiotics
Drug Classpenam, cephamycin, cephalosporin
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsNeisseria gonorrhoeaewgs, Neisseria meningitidisg+wgs
Classification13 ontology terms | Show
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)

Resistomes

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 413 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).

Prevalence: protein variant model (view sequences)

SpeciesNCBI ChromosomeNCBI PlasmidNCBI WGSNCBI GI
Neisseria gonorrhoeae0%0%1.33%0%
Neisseria meningitidis3.82%0%19.65%0%
Show Perfect Only


Detection Models

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

Legend:

  • discovered in clinical, agricultural, or environmental isolates

  • discovered via laboratory selection experiments

  • ReSeqTB https://platform.reseqtb.org

Published Variants:

PMID: 26787702F504L
PMID: 18986991G482S
PMID: 16940068I312M V316T G545S
PMID: 25199775A501P
PMID: 25987627A510V N512Y

>gb|AAF40852.1|+|Neisseria meningititis PBP2 conferring resistance to beta-lactam [Neisseria meningitidis MC58]
MLIKSEYKPRMLPKEEQVKKPMTSNGRISFVLMAIAVLFAGLIARGLYLQTVTYNFLKEQ
GDNRIVRTQTLPATRGTVSDRNGAVLALSAPTESLFAVPKEMKEMPSAAQLERLSELVDV
PVDVLRNKLEQKGKSFIWIKRQLDPKVAEEVKALGLENFVFEKELKRHYPMGNLFAHVIG
FTDIDGKGQEGLELSLEDSLHGEDGAEVVLRDRQGNIVDSLDSPRNKAPKNGKDIILSLD
QRIQTLAYEELNKAVEYHQAKAGTVVVLDARTGEILALANTPAYDPNRPGRADSEQRRNR
AVTDMIEPGSAIKPFVIAKALDAGKTDLNERLNTQPYKIGPSPVRDTHVYPSLDVRGIMQ
KSSNVGTSKLSARFGAEEMYDFYHELGIGVRMHSGFPGETAGLLRNWRRWRPIEQATMSF
GYGLQLSLLQLARAYTALTHDGVLLPVSFEKQAVAPQGKRIFKESTAREVRNLMVSVTEP
GGTGTAGAVDGFDVGAKTGTARKFVNGRYADNKHIATFIGFAPAKNPRVIVAVTIDEPTA
HGYYGGVVAGPPFKKIMGGSLNILGISPTKPLTAAAVKTPS



>gb|AE002098.2|+|419829-421574|Neisseria meningititis PBP2 conferring resistance to beta-lactam [Neisseria meningitidis MC58]
ATGTTGATTAAGAGCGAATATAAGCCTCGGATGCTGCCCAAAGAAGAGCAGGTCAAAAAGCCGATGACCAGTAACGGACGGATCAGCTTC
GTCCTGATGGCAATAGCGGTCTTGTTTGCCGGTCTGATTGCTCGCGGACTGTATCTGCAGACGGTAACGTATAACTTTTTGAAAGAACAG
GGCGACAACCGGATTGTGCGGACTCAAACATTGCCGGCTACACGCGGTACGGTTTCGGACCGGAACGGTGCGGTTTTGGCGTTGAGTGCG
CCGACGGAGTCCCTGTTTGCCGTGCCTAAAGAGATGAAGGAAATGCCGTCTGCCGCACAATTGGAACGCCTGTCCGAGCTTGTCGATGTG
CCGGTTGATGTTTTGAGGAACAAGCTCGAACAGAAAGGCAAGTCGTTTATCTGGATTAAGCGGCAGCTCGATCCCAAGGTTGCCGAAGAG
GTCAAAGCCTTGGGTTTGGAAAACTTTGTATTTGAAAAAGAATTAAAACGCCATTACCCGATGGGCAACCTGTTTGCACACGTCATCGGA
TTTACCGATATTGACGGCAAAGGTCAGGAAGGTTTGGAACTTTCGCTTGAAGACAGCCTGCATGGCGAAGACGGCGCGGAAGTCGTTTTG
CGGGACCGGCAGGGCAATATTGTGGACAGCTTGGACTCCCCGCGCAATAAAGCCCCGAAAAACGGCAAAGACATCATCCTTTCCCTCGAT
CAGAGGATTCAGACCTTGGCCTATGAAGAGTTGAACAAGGCGGTCGAATACCATCAGGCAAAAGCCGGAACGGTGGTGGTTTTGGATGCC
CGCACGGGGGAAATCCTCGCCTTGGCCAATACGCCCGCCTACGATCCCAACAGGCCCGGCCGGGCAGACAGCGAACAGCGGCGCAACCGT
GCCGTAACCGATATGATCGAACCCGGTTCGGCAATCAAACCGTTTGTGATTGCGAAGGCATTGGATGCGGGCAAAACCGATTTGAACGAA
CGGCTGAATACGCAGCCTTATAAAATCGGACCGTCTCCCGTGCGCGATACCCATGTTTACCCCTCTTTGGATGTGCGCGGCATCATGCAG
AAATCGTCCAACGTCGGCACAAGCAAACTGTCTGCGCGTTTCGGTGCCGAAGAAATGTATGACTTCTATCATGAGTTGGGCATCGGTGTG
CGTATGCACTCGGGCTTTCCGGGCGAAACTGCAGGTTTGTTGAGAAATTGGCGCAGGTGGCGGCCTATCGAACAGGCGACGATGTCTTTC
GGTTACGGCCTGCAATTGAGCCTGCTGCAATTGGCGCGCGCCTATACCGCACTGACGCACGACGGCGTTTTACTGCCGGTCAGCTTTGAA
AAACAGGCGGTTGCGCCGCAAGGCAAACGCATATTCAAAGAATCGACCGCGCGCGAGGTACGCAATCTGATGGTTTCCGTAACCGAGCCG
GGCGGCACCGGTACGGCGGGTGCGGTGGACGGTTTCGATGTCGGCGCGAAAACCGGCACGGCGCGCAAGTTCGTCAACGGGCGTTATGCC
GACAACAAACACATCGCTACCTTTATCGGTTTTGCCCCCGCCAAAAATCCCCGTGTGATTGTGGCGGTAACCATTGACGAACCGACTGCC
CACGGTTATTACGGCGGCGTAGTGGCAGGGCCGCCCTTCAAAAAAATTATGGGCGGCAGCCTGAACATCTTGGGCATTTCCCCGACCAAG
CCACTGACCGCCGCAGCCGTCAAAACACCGTCTTAA