Document Detail


New horizons in the treatment of tuberculosis.
MedLine Citation:
PMID:  9416967     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The development of new chemotherapy for the treatment of tuberculosis has three major objectives: first, the development of faster-acting drugs to shorten the duration of treatment; second, the development of novel antimicrobials to counter the emergence of bacteria resistant to current therapies; and, third, the development of chemotherapeutics that specifically target dormant bacilli to treat the one-third of the world's population latently infected with tubercle bacilli. Strategies based upon optimizing the inhibition of known targets require an extensive knowledge of the detailed mechanism of action of current antimycobacterial agents. For many agents such as isoniazid, ethambutol, rifampin, and pyrazinamide such knowledge is now available. Strategies based upon the identification of novel targets will necessitate the identification of biochemical pathways specific to mycobacteria and related organisms. Many unique metabolic processes occur during the biosynthesis of mycobacterial cell wall components, and some attractive new targets have emerged. The development of targets specific to latency will require a detailed picture of the metabolism and biochemical pathways occurring in dormant bacilli. Recent evidence suggests that anaerobic metabolic pathways may operate in dormant bacilli, and the enzymes involved in such pathways may also provide significant new targets for intervention. The combination of the mycobacterial genome sequence that is anticipated to become available this year with an improved understanding of the unique metabolic processes that define mycobacteria as a genus offers the greatest hope for the elimination of one of mankind's oldest enemies.
Authors:
C E Barry
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  54     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-01-15     Completed Date:  1998-01-15     Revised Date:  2009-08-10    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1165-72     Citation Subset:  IM    
Affiliation:
Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, NIAID, NIH, Hamilton, MT 59840-2999, USA. clifton_barry@nih.gov
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MeSH Terms
Descriptor/Qualifier:
Animals
Drug Design
Drug Resistance, Microbial
Ethambutol / therapeutic use
Humans
Isoniazid / therapeutic use
Mycolic Acids / metabolism
Pyrazinamide / therapeutic use
Rifampin / therapeutic use
Tuberculosis / drug therapy*
Grant Support
ID/Acronym/Agency:
Z01 AI000693-15/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Mycolic Acids; 13292-46-1/Rifampin; 54-85-3/Isoniazid; 74-55-5/Ethambutol; 98-96-4/Pyrazinamide

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


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