Molecule Information

General Information of the Molecule (ID: Mol01038)

• Name: Penicillin-binding protein 2B (PBP2B) ,Streptococcus pneumoniae
• Synonyms: PBP2b; Peptidoglycan transpeptidase; pbp2b; spr1517
• Molecule Type: Protein
• Gene Name: penA
• Sequence:
  MRKFNSHSIPIRLNLLFSIVILLFMTIIGRLLYMQVLNKDFYEKKLASASQTKITSSSAR
  GEIYDASGKPLVENTLKQVVSFTRSNKMTATDLKETAKKLLTYVSISSPNLTERQLADYY
  LADPEIYKKIVEALPSEKRLDSDGNRLSESELYNNAVDSVQTSQLNYTEDEKKEIYLFSQ
  LNAVGNFATGTIATDPLNDSQVAVIASISKEMPGISISTSWDRKVLETSLSSIVGSVSSE
  KAGLPAEEAEAYLKKGYSLNDRVGTSYLEKQYEETLQGKRSVKEIHLDKYGNMESVDTIE
  EGSKGNNIKLTIDLAFQDSVDALLKSYFNSELENGGAKYSEGVYAVALNPKTGAVLSMSG
  IKHDLKTGELTPDSLGTVTNVFVPGSVVKAATISSGWENGVLSGNQTLTDQSIVFQGSAP
  INSWYTQAYGSFPITAVQALEYSSNTYMVQTALGLMGQTYQPNMFVGTSNLESAMEKLRS
  TFGEYGLGTATGIDLPDESTGFVPKEYSFANYITNAFGQFDNYTPMQLAQYVATIANNGV
  RVAPRIVEGIYGNNDKGGLGDLIQQLQPTEMNKVNISDSDMSILHQGFYQVAHGTSGLTT
  GRAFSNGALVSISGKTGTAESYVADGQQATNTNAVAYAPSDNPQIAVAVVFPHNTNLTNG
  VGPSIARDIINLYQKYHPMN
• Function: A transpeptidase that forms peptide cross-links between adjacent glycan strands in cell wall peptidoglycan (PG). Part of the elongasome machinery that synthesizes peripheral PG.
• Uniprot ID: PBP2_STRR6

Kingdom: N.A.
Phylum: Firmicutes
Class: Bacilli
Order: Lactobacillales
Family: Streptococcaceae
Genus: Streptococcus
Species: Streptococcus pneumoniae

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) 3 drug(s) in total

Amoxicillin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.T445A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.E475G
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.T488A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.A591S
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.G596P
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.N605D
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.L608T
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.G618A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.D624G
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.Q627E
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Disease Class: Streptococcus pneumoniae infection [1]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Amoxicillin
• Molecule Alteration: Missense mutation; p.T629N
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: PCR amplification and sequence alignments assay
• Experiment for Drug Resistance: Correspondence discriminant assay
• Mechanism Description: The efficacy of Beta-lactam antibiotics in Streptococcus pneumoniae has been compromised because of the development of altered penicillin-binding proteins (PBPs).

Cefprozil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Pneumocystis jirovecii infection [2], [3], [4]

• Resistant Disease: Pneumocystis jirovecii infection [ICD-11: CA40.6]
• Resistant Drug: Cefprozil
• Molecule Alteration: Missense mutation; p.T445A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.The PBP2b T445-A substitution found in all PISP and PRSP and one PSSP has been found in all low-level Beta-lactam-resistant pneumococci examined.

Disease Class: Streptococcus pneumoniae infection [2], [3], [4]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Cefprozil
• Molecule Alteration: Missense mutation; p.T445A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.The PBP2b T445-A substitution found in all PISP and PRSP and one PSSP has been found in all low-level Beta-lactam-resistant pneumococci examined.

Disease Class: Streptococcus pneumoniae infection [2], [3], [4]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Cefprozil
• Molecule Alteration: Missense mutation; p.T445A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.The PBP2b T445-A substitution found in all PISP and PRSP and one PSSP has been found in all low-level Beta-lactam-resistant pneumococci examined.

Disease Class: Streptococcus pneumoniae infection [2], [3], [4]

• Resistant Disease: Streptococcus pneumoniae infection [ICD-11: AA80.2]
• Resistant Drug: Cefprozil
• Molecule Alteration: Missense mutation; p.T445A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: MICs for and PBP affinities of the strains correlated with the changes found in the PBP active binding sites.The PBP2b T445-A substitution found in all PISP and PRSP and one PSSP has been found in all low-level Beta-lactam-resistant pneumococci examined.

Ceftobiprole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Community-acquired pneumonia [2], [3], [4]

• Resistant Disease: Community-acquired pneumonia [ICD-11: CA40.2]
• Resistant Drug: Ceftobiprole
• Molecule Alteration: Missense mutation; p.KTGTA motif p.A >G
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Streptococcus pneumoniae isolates; 1313
• Experiment for Molecule Alteration: Genome sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: Beta-Lactam resistance in S. pneumoniae is caused by mutations in the penicillin-binding domains of one or more of its six penicillin-binding proteins (PBPs) resulting from point mutations or mosaic genes. Altered PBP 1a, PBP 2x, and PBP 2b are the most important PBPs for Beta-lactam resistance among clinical isolates.

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.