Abstract | OBJECTIVE: To investigate the mechanism of the action and the target of pyrazinamide (PZA), by examining the effect of nutrient-starved conditions on PZA activity. METHODS: RESULTS: The CFU of M. tuberculosis treated with PZA for 0, 3, 5, 10 days nutrient starvation compared with their respective controls, decreased by 23.08%, 37.75%, 82.32%, 81.03%, respectively. The membrane potential of M. tuberculosis in nutrient-starved cultures declined rapidly over the first 5 days' starvation. The starved bacilli treated with PZA had significantly lower level of membrane potential compared with the control. The effect of PZA on lowering the membrane potential was antagonized by addition of glucose, which provided energy for the bacilli. Fatty acids, benzoic acid and salicylic acid-enhanced PZA activity in both normal and starved bacilli, especially in starved bacilli. CONCLUSION: Nutrient starved incubation conditions and weak acids could enhance pyrazinamide activity against Mycobacterium tuberculosis. PZA can impair Mycobacterium tuberculosis cell viability by disrupting the energy supply system and reducing membrane potential of the cells.
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Authors | Zhi-fei Chen, Qiang Huang, Yuan-yuan Li, Ying Zhang, Yi Ren, Kai-shang Li, Zhi-jun Fu, Shun-qing Xu |
Journal | Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases
(Zhonghua Jie He He Hu Xi Za Zhi)
Vol. 30
Issue 5
Pg. 359-62
(May 2007)
ISSN: 1001-0939 [Print] China |
PMID | 17651643
(Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antitubercular Agents
- Pyrazinamide
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Topics |
- Antitubercular Agents
(pharmacology)
- Membrane Potentials
- Microbial Viability
- Mycobacterium tuberculosis
(drug effects, metabolism, physiology)
- Pyrazinamide
(pharmacology)
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