Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZA(r)). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the develop...

Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug for tuberculosis which requires conversion to the bactericidal compound pyrazinoic acid by bacterial pyrazinamidase activity. Mutations leading to a loss of pyrazinamidase activity cause PZA resistance in Mycobacterium tuberculosis. Thus, the detection of pyrazinamidase activity makes the discrimination of PZA-resistant tuberculosis po...

Abstract Mechanochemical milling of ethenzamide (ETZ), a nonsteroidal anti‐inflammatory drug, with substituted aromatic carboxylic acids as well anti‐tuberculosis drug pyrazinamide (PZA) resulted in the formation eutectics. Although large number cocrystals polymorphic are reported for ETZ, first time we have synthesized six eutectics including an instance drug‐drug eutectic system. Supramolecul...

The pncA gene mutations associated with pyrazinamide (PZA) resistance in Mycobacterium tuberculosis complex were determined in 26 PZA-resistant isolates in Japan. Of the 26 PZA-resistant isolates included, 21 were negative for pyrazinamidase (PZase). Of these, 20 isolates had various pncA mutations, resulting in alteration of primary amino acid sequence. However, 1 PZase-negative isolate did no...

Relatively little is known about the hepatotoxicity of pyrazinamide (PZA). PZA requires activation by amidase to form pyrazinoic acid (PA). Xanthine oxidase then hydroxylates PA to form 5-hydroxypyrazinoic acid (5-OH-PA). PZA can also be directly oxidized to form 5-OH-PZA. Before this study, it was unclear which metabolic pathway or PZA metabolites led to hepatotoxicity. This study determines w...

A total of 76 clinical Mycobacterium tuberculosis isolates from Taiwan were tested for pyrazinamidase activity, pyrazinamide susceptibility, and pncA mutations. Frequency of resistance to PZA rose with increases in resistance to first-line drugs. Of 17 pyrazinamide-resistant strains, 7 (3 of which had not been previously described) possessed mutations in the pncA gene.

In 1952 the clinical use of pyrazinamide (PZA) was first reported by Yeager, Munroe, and Dessa&. In 1954 McCune, Tompsett, and McDermott2 observed that the combined use of isoniazid and pyrazinamide in the treatment of pulmonary tuberculosis was especially effective. Isoniazid (INH) and pyrazinamide have been employed at the San Fernando Veterans Administration Hospital since 1952, but not unti...

1 Issues in MTBC Drug Susceptibility Testing: PZA BACKGROUND Pyrazinamide (PZA) is a critical component of first-line drug combination therapy for Mycobacterium tuberculosis complex (MTBC) including both susceptible and multi-drug resistant tuberculosis (MDR TB). Inclusion of PZA has shortened the previous 9–12 month chemotherapy regimen to 6 months.1 PZA has also become an essential part of MD...

Pyrazinamide (PZA) an important drug in the anti-tuberculosis therapy, activated by an enzyme Pyrazinamidase (PZase). The basis of PZA resistance in Mycobacterium tuberculosis (Mtb) is owing to mutation in pncA gene coding for PZase. The identification of the structural or functional defects in the mutant enzymes leading to resistance still remains an area to be explored. The Wild-type (WT) and...

An analog of pyrazinamide (PZA), 5-chloropyrazinamide (5-Cl-PZA), has previously been shown to inhibit mycobacterial fatty acid synthase I (FASI). FASI has been purified from a recombinant strain of M. smegmatis (M. smegmatis Deltafas1 attB::M. tuberculosis fas1). Following purification, FASI activity and inhibition were assessed spectrophotometrically by monitoring NADPH oxidation. The observe...