Disease Information

General Information of the Disease (ID: DIS00308)

• Name: Pneumoconiosis
• ICD: ICD-11: CA60

Type(s) of Resistant Mechanism of This Disease

  DISM: Drug Inactivation by Structure Modification

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Isoniazid

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Drug Inactivation by Structure Modification (DISM)

Key Molecule: Catalase-peroxidase (KATG) [1]

• Resistant Disease: Pneumoconiosis complicated with tuberculosis [ICD-11: CA60.Y]
• Molecule Alteration: Missense mutation; p.S315T
• Resistant Drug: Isoniazid
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• In Vitro Model: Mycobacterium tuberculosis H37Rv1; 1773
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Isoniazid is a hydrazine chemical synthetic drug, which is able to be oxidized to isonicotinic acid by the catalase-peroxidase encoded by the katG gene that participates in the synthesis of coenzyme I (NAD) to inhibit the biosynthesis of mycolic acid of the cell wall in Mycobacterium tuberculosis, so as to damage the MDR-TB's barricade of resisting antioxygen and invasion. Due to deletion or mutation in the katG gene, resistance is able to be generated as the enzymatic activity is lost or degraded, thus, inhibiting the activation of Isoniazid.

Key Molecule: Catalase-peroxidase (KATG) [1]

• Resistant Disease: Pneumoconiosis complicated with tuberculosis [ICD-11: CA60.Y]
• Molecule Alteration: Missense mutation; p.S315N
• Resistant Drug: Isoniazid
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• In Vitro Model: Mycobacterium tuberculosis H37Rv1; 1773
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Isoniazid is a hydrazine chemical synthetic drug, which is able to be oxidized to isonicotinic acid by the catalase-peroxidase encoded by the katG gene that participates in the synthesis of coenzyme I (NAD) to inhibit the biosynthesis of mycolic acid of the cell wall in Mycobacterium tuberculosis, so as to damage the MDR-TB's barricade of resisting antioxygen and invasion. Due to deletion or mutation in the katG gene, resistance is able to be generated as the enzymatic activity is lost or degraded, thus, inhibiting the activation of Isoniazid.

Key Molecule: Catalase-peroxidase (KATG) [1]

• Resistant Disease: Pneumoconiosis complicated with tuberculosis [ICD-11: CA60.Y]
• Molecule Alteration: Missense mutation; p.A431V
• Resistant Drug: Isoniazid
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Mycobacterium tuberculosis isolates; 1773
• In Vitro Model: Mycobacterium tuberculosis H37Rv1; 1773
• Experiment for Molecule Alteration: qRT-PCR
• Mechanism Description: Isoniazid is a hydrazine chemical synthetic drug, which is able to be oxidized to isonicotinic acid by the catalase-peroxidase encoded by the katG gene that participates in the synthesis of coenzyme I (NAD) to inhibit the biosynthesis of mycolic acid of the cell wall in Mycobacterium tuberculosis, so as to damage the MDR-TB's barricade of resisting antioxygen and invasion. Due to deletion or mutation in the katG gene, resistance is able to be generated as the enzymatic activity is lost or degraded, thus, inhibiting the activation of Isoniazid.

Silicon dioxide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: HOX transcript antisense RNA (HOTAIR) [2]

• Resistant Disease: Silicosis [ICD-11: CA60.0Z]
• Molecule Alteration: Up-regulation; Interaction
• Resistant Drug: Silicon dioxide
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: MRC-5 cells; Lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: NIH/3T3 cells; Whole embryo; Mus musculus (Mouse); CVCL_0594
• In Vitro Model: HBE cells; Bronchus; Homo sapiens (Human); CVCL_0287
• In Vivo Model: Silica-Induced lung Fibrosis mouse model; Lung Fibrosis MiR-326 overexpression mouse model; Mus musculus
• Experiment for Molecule Alteration: Western bloting analysis; Immunofluorescence assay; Knockdown assay
• Experiment for Drug Resistance: Dual luciferase reporter assays
• Mechanism Description: miR-326 Inhibits Inflammation and Promotes Autophagy in Silica-Induced Pulmonary Fibrosis through Targeting TNFSF14 and PTBP1.

References

• Ref 1: Analysis of mutational characteristics of the drug-resistant gene katG in multi-drug resistant Mycobacterium tuberculosis L-form among patients with pneumoconiosis complicated with tuberculosis .Mol Med Rep. 2014 May;9(5):2031-5. doi: 10.3892/mmr.2014.2045. Epub 2014 Mar 13. 10.3892/mmr.2014.2045
• Ref 2: Andrographolide antagonizes the cigarette smoke-induced epithelial-mesenchymal transition and pulmonary dysfunction through anti-inflammatory inhibiting HOTAIRToxicology. 2019 Jun 15;422:84-94. doi: 10.1016/j.tox.2019.05.009. Epub 2019 May 23.