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Articles

Mechanism by Which Hydnocarpic Acid Inhibits Mycobacterial Multiplication

Peter L. Jacobsen, Louis Levy
Peter L. Jacobsen
1Leprosy Research Unit, Public Health Service Hospital, San Francisco, California 94118
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Louis Levy
1Leprosy Research Unit, Public Health Service Hospital, San Francisco, California 94118
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DOI: 10.1128/AAC.3.3.373
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ABSTRACT

Recent work in this laboratory has shown that hydnocarpic acid (HA), a principal constituent of chaulmoogra oil, inhibits multiplication in vitro of a number of mycobacterial species. This activity of HA was not shared by several straight-chain fatty acids and by dihydrochaulmoogric acid. A study of the interaction of HA with biotin has been undertaken, based on a structural analogy between biotin and the cyclopentenyl fatty acid. The multiplication of a strain of Mycobacterium intracellulare susceptible to 2 μg of HA/ml was measured turbidimetrically in Dubos medium, in the presence and absence of biotin and several other compounds. Biotin and, to a lesser extent, adenine plus guanine, palmitic acid, and linoleic acid antagonized growth inhibition by HA. Desthiobiotin, thioctic acid, and succinic acid did not block inhibition of bacterial multiplication by HA. HA may act by blocking the coenzymatic activity of biotin, or it may inhibit microbial biotin synthesis. Resumption of multiplication of M. intracellulare after a period of inhibition by HA in broth culture was found to be accompanied by reduction of the effective concentration of the drug; this could have resulted from metabolism of HA or production of an antagonist to HA by the organisms. Also, those organisms that multiplied in the presence of HA were found to represent HA-resistant mutants of M. intracellulare.

  • Copyright © 1973 American Society for Microbiology
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Mechanism by Which Hydnocarpic Acid Inhibits Mycobacterial Multiplication
Peter L. Jacobsen, Louis Levy
Antimicrobial Agents and Chemotherapy Mar 1973, 3 (3) 373-379; DOI: 10.1128/AAC.3.3.373

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Mechanism by Which Hydnocarpic Acid Inhibits Mycobacterial Multiplication
Peter L. Jacobsen, Louis Levy
Antimicrobial Agents and Chemotherapy Mar 1973, 3 (3) 373-379; DOI: 10.1128/AAC.3.3.373
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