Pyrazinamide: the importance of uncovering the mechanisms of action in mycobacteria.

摘要: Pyrazinamide (PZA) is still one of the key drugs used in current therapeutic regimens for tuberculosis (TB). Despite its importance TB therapy, mode action PZA remains unknown. has to be converted active form pyrazinoic acid (POA) by nicotinamidase PncA and then excreted an unknown efflux pump. At acidic conditions, POA protonated HPOA reabsorbed into cell where it causes cellular damage. For a long time, been thought that PZA/POA no defined target action, but recent studies have shown both several different targets interfering with diverse biochemical pathways, especially NAD(+) energy metabolism. resistance seems depend not only on defective pyrazinamidase also rather result interplay many enzyme transport mechanisms.