Isoniazid metabolism and binding by sensitive and resistant strains of Mycobacterium smegmatis
| Autor: | George Ling, David Fishbain, Donn J. Kushner |
|---|---|
| Rok vydání: | 1972 |
| Předmět: |
Glycerol
Azides Immunology Isonicotinic acid Hydroxylamines Applied Microbiology and Biotechnology Microbiology Mycobacterium chemistry.chemical_compound Bacterial Proteins Genetics medicine Isoniazid heterocyclic compounds Hydrazine (antidepressant) RNA Messenger Molecular Biology Carbon Isotopes Cyanides biology Chemistry Mycobacterium smegmatis Temperature Drug Resistance Microbial General Medicine Metabolism biochemical phenomena metabolism and nutrition respiratory system bacterial infections and mycoses biology.organism_classification respiratory tract diseases Culture Media Chloramphenicol Hydrazines Biochemistry Spectrophotometry Isonicotinic Acids medicine.drug Toluene |
| Zdroj: | Canadian journal of microbiology. 18(6) |
| ISSN: | 0008-4166 |
| Popis: | Suspensions of Mycobacterium smegmatis in buffer broke down isoniazid (INH) after a lag period and produced equivalent amounts of isonicotinic acid (INA). Smaller amounts of hydrazine were formed. If chloramphenicol (CAP) was added at the beginning of the incubation, INH did not disappear nor did INA or hydrazine appear. However, if CAP was added after INH had started to disappear, the fall in INH and the appearance of INA were the same as in the absence of CAP, and more hydrazine was formed. Sensitive and resistant cells caused similar reactions, except that the former produced somewhat more hydrazine. These results, and others with toluene-treated cells, suggest that INH is broken down by at least two induced enzymes, one of which splits INH to INA and hydrazine, and a second enzyme(s) which changes hydrazine to an unknown product. Lowering the incubation temperature slowed metabolic changes. Glycerol increased the rate of INH breakdown. Cyanide and azide inhibited breakdown. Azide had a much greater effect on INH-sensitive than on INH-resistant cells. Sensitive cells bound about twice as much radioactivity from 14C-labeled INH as resistant cells. Effects of temperature, metabolites, and inhibitors on binding were also studied. These experiments show that INH does not act as an inhibitor of protein synthesis or mRNA synthesis in sensitive cells and that resistant cells are permeable to INH, even though they bind less of the drug than sensitive cells.Isoniazid-sensitive and resistant strains were about equally susceptible to the growth-inhibitory action of hydrazine and hydroxylamine. Neither was inhibited by INA. During incubation of sensitive cells with INH in growth media very small amounts of hydrazine were formed, insufficient to inhibit growth. Resistant cells grew in the presence of INH without destroying significant amounts of it. Apparently INH itself, and not a metabolic product, is the inhibitory substance. Resistance does not depend on INH destruction. |
| Databáze: | OpenAIRE |
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