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Enters mycobacterial cells in a concentration-dependent manner, binds to the beta-subunit of DNA-dependent RNA polymerase, forms a stable drug-enzyme complex, and suppresses RNA synthesis by inhibiting the elongation of messenger RNA
- Enters mycobacterial cells in a concentration-dependent manner, binds to the beta-subunit of DNA-dependent RNA polymerase, forms a stable drug-enzyme complex, and suppresses RNA synthesis by inhibiting the elongation of messenger RNA.
- Unclear, is thought to include 1) the inhibition of fatty acid synthase type I in replicating bacilli leading to interference with mycolic acid synthesis, 2) disruption of cellular membrane transport, and 3) reduction of intracellular pH.
- Diffuses into bacterial cells where it is activated by KatG (an oxidase/peroxidase encoded by the gene katG) to the nicotinoyl radical, which reacts with NAD+ of NADP+ to produce active adducts, the adducts interfere with the synthesis of mycolic acids by inhibiting NADH-dependent enoyl-ACP reductase, which is encoded by the gene inhA.
- inhibits arabinosyl transferase III, which is involved in cell-wall biosynthesis; this results in interference with the biosynthesis of the cell wall component arabinogalactan.
- target 50S ribosomal subunit on RNA, inhibiting peptidyl transferase.
- Inhibits DNA synthesis and supercoiling by targeting topoisomerase.
- blocks formation of the 70S initiation complex in peptide synthesis.
- Its an analogue of D-alanine that inhibits peptidoglycan synthesis by blocking the action of D-Alanine:D-Alanine ligase (Ddl), it also inhibits D-alanine racemase (Alr), which is involved in the conversion of L-Alanine to D-Alanine, which then serves as a substrate for Ddl.
- A structural analog of PABA and acts as a competitive inhibitor of dihydropteroate synthase (DHPS) in the bacterial folate pathway.
- Unknown, but may involve cellular membrane disruption, inhibition of mycobacterial phospholipase A2, inhibition of microbial potassium transport generation of hydrogen peroxide, and interference with bacterial electron transport systems.
- Inhibits protein synthesis by targeting the 30S ribosomal subunit.
Expert Solution
- Rifamycins
Enters mycobacterial cells in a concentration-dependent manner, binds to the beta-subunit of DNA-dependent RNA polymerase, forms a stable drug-enzyme complex, and suppresses RNA synthesis by inhibiting the elongation of messenger RNA.
- Pyrazinamide
Unclear, is thought to include 1) the inhibition of fatty acid synthase type I in replicating bacilli leading to interference with mycolic acid synthesis, 2) disruption of cellular membrane transport, and 3) reduction of intracellular pH.
- Isoniazid
Diffuses into bacterial cells where it is activated by KatG (an oxidase/peroxidase encoded by the gene katG) to the nicotinoyl radical, which reacts with NAD+ of NADP+ to produce active adducts, the adducts interfere with the synthesis of mycolic acids by inhibiting NADH-dependent enoyl-ACP reductase, which is encoded by the gene inhA.
- Ethambutol
inhibits arabinosyl transferase III, which is involved in cell-wall biosynthesis; this results in interference with the biosynthesis of the cell wall component arabinogalactan.
- Macrolides
target 50S ribosomal subunit on RNA, inhibiting peptidyl transferase.
- Fluoroquinolones
Inhibits DNA synthesis and supercoiling by targeting topoisomerase.
- Linezolid
blocks formation of the 70S initiation complex in peptide synthesis.
- Cycloserine
Its an analogue of D-alanine that inhibits peptidoglycan synthesis by blocking the action of D-Alanine:D-Alanine ligase (Ddl), it also inhibits D-alanine racemase (Alr), which is involved in the conversion of L-Alanine to D-Alanine, which then serves as a substrate for Ddl.
- Dapsone
A structural analog of PABA and acts as a competitive inhibitor of dihydropteroate synthase (DHPS) in the bacterial folate pathway.
- Clofazimine
Unknown, but may involve cellular membrane disruption, inhibition of mycobacterial phospholipase A2, inhibition of microbial potassium transport generation of hydrogen peroxide, and interference with bacterial electron transport systems.
- Streptomycin
Inhibits protein synthesis by targeting the 30S ribosomal subunit.
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