Molecule Information

General Information of the Molecule (ID: Mol01054)

• Name: Probable peptidoglycan D,D-transpeptidase PenA (PENA) ,Neisseria gonorrhoeae
• Synonyms: Penicillin-binding protein 2; PBP-2
• Molecule Type: Protein
• Gene Name: penA
• Sequence:
  MLIKSEYKPRMLPKEEQVKKPMTSNGRISFVLMAMAVLFACLIARGLYLQTVTYNFLKEQ
  GDNRIVRTQALPATRGTVSDRNGAVLALSAPTESLFAVPKDMKEMPSAAQLERLSELVDV
  PVDVLRNKLEQKGKSFIWIKRQLDPKVAEEVKALGLENFVFEKELKRHYPMGNLFAHVIG
  FTDIDGKGQEGLELSLEDSLYGEDGAEVVLRDRQGNIVDSLDSPRNKAPQNGKDIILSLD
  QRIQTLAYEELNKAVEYHQAKAGTVVVLDARTGEILALANTPAYDPNRPGRADSEQRRNR
  AVTDMIEPGSAIKPFVIAKALDAGKTDLNERLNTQPYKIGPSPVRDTHVYPSLDVRGIMQ
  KSSNVGTSKLSARFGAEEMYDFYHELGIGVRMHSGFPGETAGLLRNWRRWRPIEQATMSF
  GYGLQLSLLQLARAYTALTHDGVLLPLSFEKQAVAPQGKRIFKESTAREVRNLMVSVTEP
  GGTGTAGAVDGFDVGAKTGTARKFVNGRYADNKHVATFIGFAPAKNPRVIVAVTIDEPTA
  HGYYGGVVAGPPFKKIMGGSLNILGISPTKPLTAAAVKTPS
• Function: Catalyzes cross-linking of the peptidoglycan cell wall at the division septum.
• Uniprot ID: PBP2_NEIGO

Kingdom: N.A.
Phylum: Proteobacteria
Class: Betaproteobacteria
Order: Neisseriales
Family: Neisseriaceae
Genus: Neisseria
Species: Neisseria gonorrhoeae

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 7 drug(s) in total

Cefdinir

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [1]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefdinir
• Molecule Alteration: Missense mutation; p.G545S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefdinir
• Molecule Alteration: Missense mutation; p.G545S+p.I312M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefdinir
• Molecule Alteration: Missense mutation; p.G545S+p.V316T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Cefditoren

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [1]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefditoren
• Molecule Alteration: Missense mutation; p.G545S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefditoren
• Molecule Alteration: Missense mutation; p.G545S+p.I312M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefditoren
• Molecule Alteration: Missense mutation; p.G545S+p.V316T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Cefixime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefixime
• Molecule Alteration: Missense mutation; p.A311V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefixime
• Molecule Alteration: Missense mutation; p.T316P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefixime
• Molecule Alteration: Missense mutation; p.A311V+p.T316P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefixime
• Molecule Alteration: Missense mutation; p.T483S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefixime
• Molecule Alteration: Missense mutation; p.T483S+p.A311V+p.T316P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Cefotiam

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefotiam
• Molecule Alteration: Missense mutation; p.G545S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefotiam
• Molecule Alteration: Missense mutation; p.G545S+p.I312M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefotiam
• Molecule Alteration: Missense mutation; p.G545S+p.V316T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Cefpodoxime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefpodoxime
• Molecule Alteration: Missense mutation; p.G545S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefpodoxime
• Molecule Alteration: Missense mutation; p.G545S+p.I312M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Cefpodoxime
• Molecule Alteration: Missense mutation; p.G545S+p.V316T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Ceftriaxone

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Ceftriaxone
• Molecule Alteration: Missense mutation; p.A311V
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Ceftriaxone
• Molecule Alteration: Missense mutation; p.T316P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Ceftriaxone
• Molecule Alteration: Missense mutation; p.A311V+p.T316P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Ceftriaxone
• Molecule Alteration: Missense mutation; p.T483S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Disease Class: Gonococcal infection [5], [6], [7]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Ceftriaxone
• Molecule Alteration: Missense mutation; p.T483S+p.A311V+p.T316P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae FA19; 528352
• In Vitro Model: Neisseria gonorrhoeae FA6140; 528353
• Experiment for Molecule Alteration: Whole genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay; broth microdilution method assay
• Mechanism Description: The penA gene,which encodes penicillin-binding protein 2 (PBP2), from H041 (penA41) is a mosaic penA allele similar to mosaic alleles conferring intermediate-level cephalosporin resistance.Tthree novel mutations, A311V, V316P, and T483S, that, when incorporated into the mosaic penA35 allele, are responsible for essentially all of the additional resistance conferred by penA41. Two of these mutations, A311V and T316P, are located near the active-site nucleophile Ser310, in a region previously shown to harbor mutations that increase resistance, whereas the remaining mutation, T483S, is in a different location in the structure of PBP2, where it may interact with the Beta-lactam carboxylate.

Penicillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Penicillin
• Molecule Alteration: Missense mutation; p.G545S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Penicillin
• Molecule Alteration: Missense mutation; p.G545S+p.I312M
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

Disease Class: Gonococcal infection [2], [3], [4]

• Resistant Disease: Gonococcal infection [ICD-11: 1A70.0]
• Resistant Drug: Penicillin
• Molecule Alteration: Missense mutation; p.G545S+p.V316T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Neisseria gonorrhoeae isolates strain; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 49226; 485
• In Vitro Model: Neisseria gonorrhoeae strain ATCC 700825; 485
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Three mutations (G545S, I312M, and V316T) in mosaic PBP2 were identified as the amino acid substitutions responsible for reduced susceptibility to cefixime in N. gonorrhoeae.

References

• Ref 1: Positive selection in penicillin-binding proteins 1a, 2b, and 2x from Streptococcus pneumoniae and its correlation with amoxicillin resistance development. Infect Genet Evol. 2008 May;8(3):331-9. doi: 10.1016/j.meegid.2008.02.001. Epub 2008 Feb 14.
• Ref 2: Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2006 Nov;50(11):3638-45. doi: 10.1128/AAC.00626-06. Epub 2006 Aug 28.
• Ref 3: Resistance to Beta-Lactams in Neisseria ssp Due to Chromosomally Encoded Penicillin-Binding Proteins. Antibiotics (Basel). 2016 Sep 28;5(4):35. doi: 10.3390/antibiotics5040035.
• Ref 4: Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance. J Biol Chem. 2009 Jan 9;284(2):1202-12. doi: 10.1074/jbc.M805761200. Epub 2008 Nov 4.
• Ref 5: Reduced susceptibility to ceftriaxone in Neisseria gonorrhoeae is associated with mutations G542S, P551S and P551L in the gonococcal penicillin-binding protein 2. J Antimicrob Chemother. 2010 Aug;65(8):1615-8. doi: 10.1093/jac/dkq187. Epub 2010 May 28.
• Ref 6: High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure. Antimicrob Agents Chemother. 2012 Mar;56(3):1273-80. doi: 10.1128/AAC.05760-11. Epub 2011 Dec 12.
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