Effects of Pyrazinamide on Fatty Acid Synthesis by Whole Mycobacterial Cells and Purified Fatty Acid Synthase I
Open Access
- 15 April 2002
- journal article
- Published by American Society for Microbiology in Journal of Bacteriology
- Vol. 184 (8), 2167-2172
- https://doi.org/10.1128/jb.184.8.2167-2172.2002
Abstract
The effects of low extracellular pH and intracellular accumulation of weak organic acids were compared with respect to fatty acid synthesis by whole cells of Mycobacterium tuberculosis and Mycobacterium smegmatis. The profile of fatty acids synthesized during exposure to benzoic, nicotinic, or pyrazinoic acids, as well as that observed during intracellular hydrolysis of the corresponding amides, was not a direct consequence of modulation of fatty acid synthesis by these compounds but reflected the response to inorganic acid stress. Analysis of fatty acid synthesis in crude mycobacterial cell extracts demonstrated that pyrazinoic acid failed to directly modulate the fatty acid synthase activity catalyzed by fatty acid synthase I (FAS-I). However, fatty acid synthesis was irreversibly inhibited by 5-chloro-pyrazinamide in a time-dependent fashion. Moreover, we demonstrate that pyrazinoic acid does not inhibit purified mycobacterial FAS-I, suggesting that this enzyme is not the immediate target of pyrazinamide.Keywords
This publication has 60 references indexed in Scilit:
- Expression of Mycobacterium smegmatis Pyrazinamidase in Mycobacterium tuberculosis Confers Hypersensitivity to Pyrazinamide and Related AmidesJournal of Bacteriology, 2000
- Inhibition of a Mycobacterium tuberculosis β-Ketoacyl ACP Synthase by IsoniazidScience, 1998
- Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequenceNature, 1998
- Regulation of Phagosomal AcidificationJournal of Biological Chemistry, 1997
- The pncA gene from naturally pyrazinamide-resistant Mycobacterium avium encodes pyrazinamidase and confers pyrazinamide susceptibility to resistant M. tuberculosis complex organismsMicrobiology, 1997
- Pyrazinamide and Pyrazinoic Acid Activity against Tubercle Bacilli in Cultured Human Macrophages and in the BACTEC SystemThe Journal of Infectious Diseases, 1990
- Thermodynamic parameters and shape of the mycobacterial polymethylpolysaccharide-fatty acid complexBiochemistry, 1988
- The action of antituberculosis drugs in short-course chemotherapyTubercle, 1985
- Control Mechanisms for Fatty Acid Synthesis in Mycobacterium SmegmatisPublished by Wiley ,1977
- THE FATE OF MYCOBACTERIUM TUBERCULOSIS IN MOUSE TISSUES AS DETERMINED BY THE MICROBIAL ENUMERATION TECHNIQUEThe Journal of Experimental Medicine, 1956