What is InhA mutation?
inhA mutations cause low-level resistance to the drug, which means that high doses of INH may be effective against M. tuberculosis. 6,7. As ETH is a structural analogue of INH, cross-resistance occurs between INH and ETH.
What is the function of InhA?
InhA plays a key role in the synthesis of fatty acids, particularly in M. tuberculosis which, has type one fatty acid synthesis (FASI) and type two fatty acid synthesis (FASII) which together function in the synthesis of mycolic acids.
What is katG gene?
tuberculosis catalase-peroxidase enzyme (KatG), encoded by the katG gene to generate a range of highly reactive species for bactericidal activity.
What is the mechanism of action of isoniazid?
Mechanism of action — The antimicrobial activity of INH is selective for mycobacteria, likely due to its ability to inhibit mycolic acid synthesis, which interferes with cell wall synthesis, thereby producing a bactericidal effect [1].
Which gene is responsible for isoniazid mechanism?
The major mechanism of INH resistance is mutation in katG, encoding the activator of INH. One specific KatG variant, S315T, is found in 94% of INH-resistant clinical isolates.
How does isoniazid resistance occur?
In addition to katG mutations, isoniazid resistance arises from mutations in the promoter region of inhA, which lead to overexpression of isoniazid’s target InhA, requiring higher doses of the drug to achieve complete inhibition3.
What does Enoyl ACP reductase do?
Enoyl-acyl carrier protein (ACP) reductases (ENRs) catalyze the last step of the elongation cycle in the synthesis of fatty acids. Fatty acid biosynthesis is essential for survival in mammals, plants, fungi and bacteria (the archaea make isoprenoid-based lipids).
What is the mechanism of action of pyrazinamide?
The mechanism of action for PZA is unknown [2,3]. The parent compound enters the bacterium passively and is metabolized via pyrazinamidase (PZase) within the cytoplasm to pyrazinoic acid; pyrazinoic acid is the active form of the drug [4].
What is KatG tuberculosis?
Mycobacterium tuberculosis catalase-peroxidase (KatG) is a bifunctional hemoprotein that has been shown to activate isoniazid (INH), a pro-drug that is integral to frontline antituberculosis treatments.
What does catalase-peroxidase do?
Catalase peroxidases (Kat) are enzyme systems that efficiently protect the bacterium from ROS damage and are used to detoxify H2O2.
What enzyme does isoniazid inhibit?
Isoniazid (INH) inhibits a specific enzyme, InhA, in the synthetic pathway of mycolic acid, a key component of the cell wall of M. tuberculosis.
Which enzyme is responsible for isoniazid metabolism in the bacterial cell?
Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex.
Is Mycobacterium tuberculosis resistant to isoniazid?
Isoniazid (INH) is the cornerstone of tuberculosis (TB) chemotherapy, used for both treatment and prophylaxis of TB. The antimycobacterial activity of INH was discovered in 1952, and almost as soon as its activity was published, the first INH-resistant Mycobacterium tuberculosis strains were reported.
How do you know if TB is drug-resistant?
Drug resistance can be detected using special laboratory tests which test the bacteria for sensitivity to the drugs or detect resistance patterns. These tests can be molecular in type (such as Xpert MTB/RIF) or else culture-based.
What is an Enoyl group?
Definition: Acyl groups derived from alkenoic acids.
Why is pyrazinamide called Z?
Pyrazinamide is an antituberculosis agent used as a component of tuberculosis (TB) treatment. A pyrazine that is used therapeutically as an antitubercular agent.
What is another name for pyrazinamide?
Pyrazinamide
| Clinical data | |
|---|---|
| Trade names | Rifater, Tebrazid, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682402 |
| License data | US DailyMed: Pyrazinamide |
What is INH a gene?
Isoniazid (isonicotinic acid hydrazide, INH) is one of the most widely used antituberculosis drugs, yet its precise target of action on Mycobacterium tuberculosis is unknown. A missense mutation within the mycobacterial inhA gene was shown to confer resistance to both INH and ethionamide (ETH) in M.