Document Detail


Iron enhances the antituberculous activity of pyrazinamide.
MedLine Citation:
PMID:  14729751     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Pyrazinamide is a paradoxical frontline tuberculosis drug characterized by high in vivo sterilizing activity but poor in vitro activity. This separation in pyrazinamide activity reflects differences between the in vivo tissue environment and in vitro culture conditions. The well-known acid pH requirement for pyrazinamide activity was discovered previously based on such reasoning but does not completely explain the discrepancy between in vivo and in vitro activity of pyrazinamide. This study examined the effect of iron, which could potentially be elevated in local inflammatory lesions, on pyrazinamide activity in vitro. MATERIALS AND METHODS: The effect of iron on the activity of pyrazinamide or its active derivative pyrazinoic acid against Mycobacterium tuberculosis was assessed in liquid medium in a drug exposure assay or in solid medium with pyrazinamide plus iron or pyrazinamide alone. The effect of iron on pyrazinamide or pyrazinoic acid was expressed as percentage of growth inhibition. RESULTS: We have shown that iron enhances the activity of pyrazinamide and pyrazinoic acid against M. tuberculosis in both liquid and solid media at acid pH 5.6. Iron enhanced the activity of pyrazinoic acid but not pyrazinamide against the naturally pyrazinamide-resistant Mycobacterium bovis BCG. Other metal ions such as magnesium, calcium and zinc did not enhance the activity of pyrazinamide or pyrazinoic acid. CONCLUSIONS: Iron increased the activity of pyrazinamide or pyrazinoic acid against M. tuberculosis in vitro. These findings may have implications for the study of mechanism of action of pyrazinamide and possible iron supplement for improving the activity of pyrazinamide.
Authors:
Akos Somoskovi; Mary Margaret Wade; Zhonghe Sun; Ying Zhang
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.     Date:  2004-01-16
Journal Detail:
Title:  The Journal of antimicrobial chemotherapy     Volume:  53     ISSN:  0305-7453     ISO Abbreviation:  J. Antimicrob. Chemother.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-02-02     Completed Date:  2004-04-20     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7513617     Medline TA:  J Antimicrob Chemother     Country:  England    
Other Details:
Languages:  eng     Pagination:  192-6     Citation Subset:  IM    
Affiliation:
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. yzhang@jhsph.edu
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MeSH Terms
Descriptor/Qualifier:
Antitubercular Agents / pharmacology*
Calcium / pharmacology
Culture Media
Drug Synergism
Hydrogen-Ion Concentration
Iron / pharmacology*
Magnesium / pharmacology
Microbial Sensitivity Tests
Mycobacterium tuberculosis / drug effects*
Pyrazinamide / analogs & derivatives*,  pharmacology*
Zinc / pharmacology
Grant Support
ID/Acronym/Agency:
AI44063/AI/NIAID NIH HHS; AI49485/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antitubercular Agents; 0/Culture Media; 7439-89-6/Iron; 7439-95-4/Magnesium; 7440-66-6/Zinc; 7440-70-2/Calcium; 98-96-4/Pyrazinamide; 98-97-5/pyrazinoic acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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