Molecule Information

General Information of the Molecule (ID: Mol01036)

• Name: Penicillin-binding protein 1A (PBP1A) ,Streptococcus pneumoniae
• Synonyms: PBP-1A; Exported protein 2; Peptidoglycan TGase; DD-transpeptidase; exp2; ponA; spr0329
• Molecule Type: Protein
• Gene Name: pbpA
• Gene ID: 60234246
• Sequence:
  MNKPTILRLIKYLSISFLSLVIAAIVLGGGVFFYYVSKAPSLSESKLVATTSSKIYDNKN
  QLIADLGSERRVNAQANDIPTDLVKAIVSIEDHRFFDHRGIDTIRILGAFLRNLQSNSLQ
  GGSALTQQLIKLTYFSTSTSDQTISRKAQEAWLAIQLEQKATKQEILTYYINKVYMSNGN
  YGMQTAAQNYYGKDLNNLSLPQLALLAGMPQAPNQYDPYSHPEAAQDRRNLVLSEMKNQG
  YISAEQYEKAVNTPITDGLQSLKSASNYPAYMDNYLKEVINQVEEETGYNLLTTGMDVYT
  NVDQEAQKHLWDIYNTDEYVAYPDDELQVASTIVDVSNGKVIAQLGARHQSSNVSFGINQ
  AVETNRDWGSTMKPITDYAPALEYGVYESTATIVHDEPYNYPGTNTPVYNWDRGYFGNIT
  LQYALQQSRNVPAVETLNKVGLNRAKTFLNGLGIDYPSIHYSNAISSNTTESDKKYGASS
  EKMAAAYAAFANGGTYYKPMYIHKVVFSDGSEKEFSNVGTRAMKETTAYMMTDMMKTVLS
  YGTGRNAYLAWLPQAGKTGTSNYTDEEIENHIKTSQFVAPDELFAGYTRKYSMAVWTGYS
  NRLTPLVGNGLTVAAKVYRSMMTYLSEGSNPEDWNIPEGLYRNGEFVFKNGARSTWSSPA
  PQQPPSTESSSSSSDSSTSQSSSTTPSTNNSTTTNPNNNTQQSNTTPDQQNQNPQPAQP
• Function: Cell wall formation.
• Uniprot ID: PBPA_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) 2 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.S351A
• 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.S575T
• 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.N609D
• 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.E512K
• 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).

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; STMK motif p.T >A +SRNVP motif p.P >T
• 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.