Neisseria gonorrhoeae PBP2 conferring resistance to beta-lactam antibiotics

Accession ARO:3004832
Synonym(s)penA
CARD Short NameNgon_PBP2_BLA
DefinitionPBP2 is a penicillin-binding protein and beta-lactam resistance enzyme encoded by the penA gene, due to mutations can cause resistance to various drugs such as Penicillin and Ceftriaxone.
AMR Gene FamilyPenicillin-binding protein mutations conferring resistance to beta-lactam antibiotics
Drug Classpenam, cephamycin, cephalosporin
Resistance Mechanismantibiotic target alteration
Resistomes with Sequence VariantsNeisseria gonorrhoeaeg+p+wgs, Neisseria meningitidiswgs
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

Unemo M, et al. 2012. Antimicrob. Agents Chemother. 56(3):1273-80 High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. (PMID 22155830)

Tomberg J, et al. 2013. Antimicrob. Agents Chemother. 57(7):3029-36 Identification of amino acids conferring high-level resistance to expanded-spectrum cephalosporins in the penA gene from Neisseria gonorrhoeae strain H041. (PMID 23587946)

Kubanova AA, et al. . Mol. Biol. (Mosk.) 48(6):977-82 [The role of some individual amino acid substitutions in penicillin-binding protein (PBP2) of Neisseria gonorrhoeae in the emergence of resistance to ceftriaxone]. (PMID 25845238)

Whiley DM, et al. 2010. J. Antimicrob. Chemother. 65(8):1615-8 Reduced susceptibility to ceftriaxone in Neisseria gonorrhoeae is associated with mutations G542S, P551S and P551L in the gonococcal penicillin-binding protein 2. (PMID 20511367)

Fedarovich A, et al. 2014. Biochemistry 53(48):7596-603 Structural effect of the Asp345a insertion in penicillin-binding protein 2 from penicillin-resistant strains of Neisseria gonorrhoeae. (PMID 25403720)

Singh AE, et al. 2021. Emerg Infect Dis 27(6):1718-1722 Molecular Characterization and Antimicrobial Resistance in Neisseria gonorrhoeae, Nunavut Region of Inuit Nunangat, Canada, 2018-2019. (PMID 34013864)

Resistomes

Prevalence of Neisseria gonorrhoeae PBP2 conferring resistance to beta-lactam antibiotics 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 gonorrhoeae70%1.02%69.22%0%
Neisseria meningitidis0%0%0.32%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: 22155830A501P A501V A501T
PMID: 23587946A311V V316P T483S
PMID: 25845238F504L A510V A516G
PMID: 20511367G542S P551S P551L
PMID: 25403720+D345
PMID: 34013864N513Y G545S

>gb|AAA25463.1|+|Neisseria gonorrhoeae PBP2 conferring resistance to beta-lactam antibiotics [Neisseria gonorrhoeae]
MLIKSEYKPRMLPKEEQVKKPMTSNGRISFVLMAMAVLFACLIARGLYLQTVTYNFLKEQ
GDNRIVRTQALPATRGTVSDRNGAVLALSAPTESLFAVPKDMKEMPSAAQLERLSELVDV
PVDVLRNKLEQKGKSFIWIKRQLDPKVAEEVKALGLENFVFEKELKRHYPMGNLFAHVIG
FTDIDGKGQEGLELSLEDSLYGEDGAEVVLRDRQGNIVDSLDSPRNKAPQNGKDIILSLD
QRIQTLAYEELNKAVEYHQAKAGTVVVLDARTGEILALANTPAYDPNRPGRADSEQRRNR
AVTDMIEPGSAIKPFVIAKALDAGKTDLNERLNTQPYKIGPSPVRDTHVYPSLDVRGIMQ
KSSNVGTSKLSARFGAEEMYDFYHELGIGVRMHSGFPGETAGLLRNWRRWRPIEQATMSF
GYGLQLSLLQLARAYTALTHDGVLLPLSFEKQAVAPQGKRIFKESTAREVRNLMVSVTEP
GGTGTAGAVDGFDVGAKTGTARKFVNGRYADNKHVATFIGFAPAKNPRVIVAVTIDEPTA
HGYYGGVVAGPPFKKIMGGSLNILGISPTKPLTAAAVKTPS



>gb|M32091.1|+|103-1848|Neisseria gonorrhoeae PBP2 conferring resistance to beta-lactam antibiotics [Neisseria gonorrhoeae]
ATGTTGATTAAAAGCGAATATAAGCCCCGGATGCTGCCCAAAGAAGAGCAGGTCAAAAAGCCGATGACCAGTAACGGACGGATTAGCTTC
GTCCTGATGGCAATGGCGGTCTTGTTTGCCTGTCTGATTGCCCGCGGGCTGTATCTGCAGACGGTAACGTATAACTTTTTGAAAGAACAG
GGCGACAACCGGATTGTGCGGACTCAAGCATTGCCGGCTACACGCGGTACGGTTTCGGACCGGAACGGTGCGGTTTTGGCGTTGAGCGCG
CCGACGGAGTCCCTGTTTGCCGTGCCTAAAGATATGAAGGAAATGCCGTCTGCCGCCCAATTGGAACGCCTGTCCGAGCTTGTCGATGTG
CCGGTCGATGTTTTGAGGAACAAACTCGAACAGAAAGGCAAGTCGTTTATTTGGATCAAGCGGCAGCTCGATCCCAAGGTTGCCGAAGAG
GTCAAAGCCTTGGGTTTGGAAAACTTTGTATTTGAAAAAGAATTAAAACGCCATTACCCGATGGGCAACCTGTTTGCACACGTCATCGGA
TTTACCGATATTGACGGCAAAGGTCAGGAAGGTTTGGAACTTTCGCTTGAAGACAGCCTGTATGGCGAAGACGGCGCGGAAGTTGTTTTG
CGGGACCGGCAGGGCAATATTGTGGACAGCTTGGACTCCCCGCGCAATAAAGCACCGCAAAACGGCAAAGACATCATCCTTTCCCTCGAT
CAGAGGATTCAGACCTTGGCCTATGAAGAGTTGAACAAGGCGGTCGAATACCATCAGGCAAAAGCCGGAACGGTGGTGGTTTTGGATGCC
CGCACGGGGGAAATCCTCGCCTTGGCCAATACGCCCGCCTACGATCCCAACAGACCCGGCCGGGCAGACAGCGAACAGCGGCGCAACCGT
GCCGTAACCGATATGATCGAACCTGGTTCGGCAATCAAACCGTTCGTGATTGCGAAGGCATTGGATGCGGGCAAAACCGATTTGAACGAA
CGGCTGAATACGCAGCCTTATAAAATCGGACCGTCTCCCGTGCGCGATACCCATGTTTACCCCTCTTTGGATGTGCGCGGCATTATGCAG
AAATCGTCCAACGTCGGCACAAGCAAACTGTCTGCGCGTTTCGGCGCCGAAGAAATGTATGACTTCTATCATGAATTGGGCATCGGTGTG
CGTATGCACTCGGGCTTTCCGGGGGAAACTGCAGGTTTGTTGAGAAATTGGCGCAGGTGGCGGCCCATCGAACAGGCGACGATGTCTTTC
GGTTACGGTCTGCAATTGAGCCTGCTGCAATTGGCGCGCGCCTATACCGCACTGACGCACGACGGCGTTTTGCTGCCGCTCAGCTTTGAG
AAGCAGGCGGTTGCGCCGCAAGGCAAACGCATATTCAAAGAATCGACCGCGCGCGAGGTACGCAATCTGATGGTTTCCGTAACCGAGCCG
GGCGGCACCGGTACGGCGGGTGCGGTGGACGGTTTCGATGTCGGCGCTAAAACCGGCACGGCGCGCAAGTTCGTCAACGGGCGTTATGCC
GACAACAAACACGTCGCTACCTTTATCGGTTTTGCCCCCGCCAAAAACCCCCGTGTGATTGTGGCGGTAACCATCGACGAACCGACTGCC
CACGGCTATTACGGCGGCGTAGTGGCAGGGCCGCCCTTCAAAAAAATTATGGGCGGCAGCCTGAACATCTTGGGCATTTCCCCGACCAAG
CCACTGACCGCCGCAGCCGTCAAAACACCGTCTTAA