Revisiting Anti-tuberculosis Activity of Pyrazinamide in Mice
- Corresponding Author:
- Jacques H. Grosset
Center for Tuberculosis Research
Johns Hopkins University School of Medicine
Baltimore, Maryland, USA
E-mail: [email protected]
Received Date: January 28, 2014; Accepted Date: March 18, 2014; Published Date: April 05, 2014
Citation: Almeida DV, Tyagi S, Li SY, Wallengren K, Pym AS, et al. (2014) Revisiting Anti-tuberculosis Activity of Pyrazinamide in Mice. J Mycobac Dis 4:145. doi:10.4172/2161-1068.1000145
Copyright: © 2014 Almeida DV, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the riginal author and source are credited.
The mechanism of action of pyrazinamide, a key sterilizing drug in the treatment of tuberculosis, remains elusive; pyrazinamide is a pro-drug that requires activation by a bacterial-encoded enzyme, and its activity is most apparent on non-replicating Mycobacterium tuberculosis. Recently, it has been suggested that pyrazinamide might exert also some host-directed effect in addition to its antimicrobial activity. To address this possibility, three sequential experiments were conducted in immune-competent BALB/c and in immune-deficient, athymic nude mice. In the first experiment, BALB/c mice infected with M. bovis, which is naturally resistant to pyrazinamide because it is unable to activate the drug, were treated with standard drug regimens with and without pyrazinamide to specifically detect a host-directed effect. As no effect was observed, pyrazinamide activity was compared in M. tuberculosis-infected BALB/c and nude mice to determine whether the effect of pyrazinamide would be reduced in the immune deficient mice. As pyrazinamide did not appear to have any affect in the nude mice, a third experiment was performed in which rifampin was replaced with rifapentine (a similar drug with a longer half-life) to permanently suppress mycobacterial growth. In these experimental conditions, the antimicrobial effect of pyrazinamide was clear. Therefore, the results of our studies rule out a significant host-directed effect of pyrazinamide in the TB infected host.