Disease Information

General Information of the Disease (ID: DIS00013)

• Name: Pseudomonas aeruginosa infection
• ICD: ICD-11: 1A0Y

Type(s) of Resistant Mechanism of This Disease

  ADTT: Aberration of the Drug's Therapeutic Target

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

Cefepime

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; p.G27D+p.A97V+p.V205L
• Resistant Drug: Cefepime
• 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.

Key Molecule: Beta-lactamase (BLA) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; p.K108E
• Resistant Drug: Cefepime
• 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)

Key Molecule: Beta-lactamase (BLA) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; p.G27D+p.A97V+p.T105A+p.V205L
• Resistant Drug: Ceftazidime
• 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.

Key Molecule: Beta-lactamase (BLA) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; p.T105A
• Resistant Drug: Ceftazidime
• 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.

Key Molecule: Beta-lactamase (BLA) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; p.T105A+p.K108E
• Resistant Drug: Ceftazidime
• 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.

Key Molecule: Beta-lactamase (BLA) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; p.R79Q+p.T105A
• Resistant Drug: Ceftazidime
• 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.

Edetic acid

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Vimentin 2, pseudogene (VIM2P) [2]

• Sensitive Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Edetic acid
• Experimental Note: Discovered Using In-vivo Testing Model
• Experiment for Molecule Alteration: Molecular modeling assay
• Experiment for Drug Resistance: Double-disk diffusion test assay
• Mechanism Description: Disk diffusion and broth microdilution methods demonstrate that unithiol inhibits native MBLs NDM-1 and VIM-2 produced by carbapenem-resistant K. pneumoniae and P. aeruginosa bacterial strains.

Unithiol

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Vimentin 2, pseudogene (VIM2P) [2]

• Sensitive Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Function; Inhibition
• Sensitive Drug: Unithiol
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Schistosoma mansoni isolates; 6183
• In Vitro Model: SH-1-V1 cells; Esophagus; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Molecular modeling assay
• Experiment for Drug Resistance: Double-disk diffusion test assay
• Mechanism Description: Disk diffusion and broth microdilution methods demonstrate that unithiol inhibits native MBLs NDM-1 and VIM-2 produced by carbapenem-resistant K. pneumoniae and P. aeruginosa bacterial strains.

Imipenem

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Beta-lactamase (BLA) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Missense mutation; p.T105A
• Resistant Drug: Imipenem
• 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: 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.
• Ref 2: Drug Repurposing of the Unithiol: Inhibition of Metallo-Beta-Lactamases for the Treatment of Carbapenem-Resistant Gram-Negative Bacterial Infections .Int J Mol Sci. 2022 Feb 6;23(3):1834. doi: 10.3390/ijms23031834. 10.3390/ijms23031834