alexa Drug-susceptible Against Tuberculosis | OMICS Group | Mycobacterial Diseases

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Drug-susceptible Against Tuberculosis

Although it is the most sterilizing drug in the armamentarium against tuberculosis (TB), an indispensable component of first-line drug combination for drug-susceptible TB and part of all recommended drug regimens for multidrug-resistant TB, pyrazinamide (PZA) remains a compound with no well-defined target of action. It is a pro-drug that needs to be activated by the mycobacterial enzyme nicotinamidase, named pyrazinamidase (PZase), to its active form, pyrazinoic acid (POA). After its activation, it is generally accepted that POA is expelled from the mycobacterial cell by an efflux pump and is protonated in the extracellular environment. Upon re-entry into the bacterial cell, this proton is released, decreasing the cytoplasmic pH and thus causing lethal damage through several possible mechanisms, including membrane disruption, inhibition of fatty acid synthetase and inhibition of trans-translation of Mycobacterium tuberculosis. In both human and mouse TB chemotherapy, the sterilizing activity of PZA becomes evident when the bacteria are not actively replicating, likely because the PZA-induced damage should accumulate.
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Last date updated on July, 2014

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