Molecule Information

General Information of the Molecule (ID: Mol00845)

• Name: Beta-lactamase (BLA) ,Pseudomonas aeruginosa
• Synonyms: Cephalosporinase; PA4110
• Molecule Type: Protein
• Gene Name: ampC
• Gene ID: 878149
• Sequence:
  MRDTRFPCLCGIAASTLLFATTPAIAGEAPADRLKALVDAAVQPVMKANDIPGLAVAISL
  KGEPHYFSYGLASKEDGRRVTPETLFEIGSVSKTFTATLAGYALTQDKMRLDDRASQHWP
  ALQGSRFDGISLLDLATYTAGGLPLQFPDSVQKDQAQIRDYYRQWQPTYAPGSQRLYSNP
  SIGLFGYLAARSLGQPFERLMEQQVFPALGLEQTHLDVPEAALAQYAQGYGKDDRPLRVG
  PGPLDAEGYGVKTSAADLLRFVDANLHPERLDRPWAQALDATHRGYYKVGDMTQGLGWEA
  YDWPISLKRLQAGNSTPMALQPHRIARLPAPQALEGQRLLNKTGSTNGFGAYVAFVPGRD
  LGLVILANRNYPNAERVKIAYAILSGLEQQGKVPLKR
• Uniprot ID: AMPC_PSEAE

Kingdom: N.A.
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Pseudomonadales
Family: Pseudomonadaceae
Genus: Pseudomonas
Species: Pseudomonas aeruginosa

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 6 drug(s) in total

Cefalotin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Pseudomonas aeruginosa infection [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Cefalotin
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: DNA sequencing and protein assay
• Experiment for Drug Resistance: Disk diffusion assay
• Mechanism Description: P. aeruginosa harbors two naturally encoded Beta-lactamase genes, one of which encodes an inducible cephalosporinase and the other of which encodes a constitutively expressed oxacillinase. AmpC is a kind of cephalosporinase which lead to drug resistance.

Cefepime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Pseudomonas aeruginosa infection [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Cefepime
• Molecule Alteration: Missense mutation; p.G27D+p.A97V+p.V205L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: PCR amplification and sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Amino acid changes G27D, A97V, and V205L in PDC-2 led to increased cefepime MICs.

Disease Class: Pseudomonas aeruginosa infection [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Cefepime
• Molecule Alteration: Missense mutation; p.K108E
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa kG2505; 287
• Experiment for Molecule Alteration: PCR amplification and sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Amino acid changes K108E in PDC-4 led to increased cefepime MICs.

Ceftazidime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Pseudomonas aeruginosa infection [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ceftazidime
• Molecule Alteration: Missense mutation; p.G27D+p.A97V+p.T105A+p.V205L
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: PCR amplification and sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The mutations compared to PDC-1 reduced susceptibility.

Disease Class: Pseudomonas aeruginosa infection [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ceftazidime
• Molecule Alteration: Missense mutation; p.T105A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa 12B; 287
• Experiment for Molecule Alteration: PCR amplification and sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The mutations compared to PDC-1 reduced susceptibility.

Disease Class: Pseudomonas aeruginosa infection [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ceftazidime
• Molecule Alteration: Missense mutation; p.T105A+p.K108E
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa kG2505; 287
• Experiment for Molecule Alteration: PCR amplification and sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The mutations compared to PDC-1 reduced susceptibility.

Disease Class: Pseudomonas aeruginosa infection [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Ceftazidime
• Molecule Alteration: Missense mutation; p.R79Q+p.T105A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa isolates; 287
• Experiment for Molecule Alteration: PCR amplification and sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: The mutations compared to PDC-1 reduced susceptibility.

Cefuroxime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Pseudomonas aeruginosa infection [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Cefuroxime
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: DNA sequencing and protein assay
• Experiment for Drug Resistance: Disk diffusion assay
• Mechanism Description: P. aeruginosa harbors two naturally encoded Beta-lactamase genes, one of which encodes an inducible cephalosporinase and the other of which encodes a constitutively expressed oxacillinase. AmpC is a kind of cephalosporinase which lead to drug resistance.

Cephaloridine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Pseudomonas aeruginosa infection [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Cephaloridine
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: DNA sequencing and protein assay
• Experiment for Drug Resistance: Disk diffusion assay
• Mechanism Description: P. aeruginosa harbors two naturally encoded Beta-lactamase genes, one of which encodes an inducible cephalosporinase and the other of which encodes a constitutively expressed oxacillinase. AmpC is a kind of cephalosporinase which lead to drug resistance.

Imipenem

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: Pseudomonas aeruginosa infection [2]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Resistant Drug: Imipenem
• Molecule Alteration: Missense mutation; p.T105A
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Pseudomonas aeruginosa PAO1; 208964
• Experiment for Molecule Alteration: PCR amplification and sequence assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: Reduced susceptibility to imipenem was related to the T105A substitution.

References

• Ref 1: Biochemical characterization of the naturally occurring oxacillinase OXA-50 of Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2004 Jun;48(6):2043-8. doi: 10.1128/AAC.48.6.2043-2048.2004.
• Ref 2: Extended-spectrum cephalosporinases in Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009 May;53(5):1766-71. doi: 10.1128/AAC.01410-08. Epub 2009 Mar 2.