Molecule Information

General Information of the Molecule (ID: Mol04266)

• Name: Pyrazinamidase ,Mycobacterium tuberculosis
• Synonyms: Pyrazinamidase
• Molecule Type: Protein

Kingdom: N.A.
Phylum: Actinobacteria
Class: Actinomycetia
Order: Corynebacteriales
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: Mycobacterium tuberculosis

Type(s) of Resistant Mechanism of This Molecule

  DISM: Drug Inactivation by Structure Modification

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Pyrazinamide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Disease Class: bifidobacterium adolescentis infection [ICD-11: XN33F] [1]

• Resistant Disease: bifidobacterium adolescentis infection [ICD-11: XN33F]
• Resistant Drug: Pyrazinamide
• Molecule Alteration: Missense mutation; Q24K+L28M+R30E+A92K
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Bifidobacterial strains; 1763
• Experiment for Molecule Alteration: PCR; Catalase foam assay; Catalase gel assay
• Experiment for Drug Resistance: Growth curve assay; Spot assay; Anti-tubercular drug uptake and surface assay; Adaptability assay; FE-SEM assay; MIC assay; Particle size assay
• Mechanism Description: The current study aims to understand the resistance of Bifidobacterium adolescentis to different anti-tubercular drugs (first-line oral tuberculosis drugs). The bacteria were grown with anti-tubercular drugs such as isoniazid, pyrazinamide, and streptomycin to better understand the resistance phenomena. It was found that even at tenfold higher concentrations, growth rates remained unchanged. In addition, a small number of bacteria were found to aggregate strongly, a property that protects against the toxicity of the drug. Further FE-SEM (Field Emission Scanning Electron Microscopy) analysis revealed that some bacteria became excessively long, elongated, and protruded on the surface. Size scattering analysis confirmed the presence of bifidobacteria in the size range of 1.0-100 um. After whole genome sequence analysis, certain mutations were found in the relevant gene. In vitro, foam formation and growth in the presence of H2O2 and HPLC (High Performance Liquid Chromatography) studies provide additional evidence for the presence of catalase. According to RAST (Rapid Annotation Using Subsystems Technology) annotation and CARD (Comprehensive Antibiotic Resistance Database analysis), there were not many components in the genome that were resistant to antibiotics. Whole genome sequence (WGS) analysis does not show the presence of bacteriocins and antibiotic resistance genes, but few hypothetical proteins were observed. 3D structure and docking studies suggest their interaction with specific ligands.

References

• Ref 1: Bifidobacterium adolescentis is resistant to pyrazinamide, isoniazid, and streptomycin. Sci Rep. 2024 Nov 28;14(1):29562.