Skip to main content
PMC home page
Applied Microbiology logoLink to Applied Microbiology
. 1970 Nov;20(5):810–814. doi: 10.1128/am.20.5.810-814.1970

Probability Distribution of Drug-Resistant Mutants in Unselected Populations of Mycobacterium tuberculosis

Hugo L David 1
PMCID: PMC377053  PMID: 4991927

Abstract

The fluctuation test shows that Mycobacterium tuberculosis mutates to resistance to isoniazid, streptomycin, ethambutol and rifampin spontaneously and at random. The average mutation rates for the drugs, in the same order, were calculated to be 2.56 × 10−8, 2.95 × 10−8, 10−7, and 2.25 × 10−10 mutation per bacterium per generation. The relatively high mutation rate to ethambutol resistance and the low mutation rate to rifampin resistance were confirmed by analyzing the increase in the proportion of mutants with time in a growing population of the tubercle bacilli. The highest proportions of mutants to be expected in unselected populations of the tubercle bacilli were calculated from the results of fluctuation tests.

Full text

PDF
813

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. CANETTI G., FROMAN S., GROSSET J., HAUDUROY P., LANGEROVA M., MAHLER H. T., MEISSNER G., MITCHISON D. A., SULA L. MYCOBACTERIA: LABORATORY METHODS FOR TESTING DRUG SENSITIVITY AND RESISTANCE. Bull World Health Organ. 1963;29:565–578. [PMC free article] [PubMed] [Google Scholar]
  2. CANETTI G., RIST N., GROSSET J. [Measurement of sensitivity of the tuberculous bacillus to antibacillary drugs by the method of proportions. Methodology, resistance criteria, results and interpretation]. Rev Tuberc Pneumol (Paris) 1963 Feb-Mar;27:217–272. [PubMed] [Google Scholar]
  3. Canetti G., Fox W., Khomenko A., Mahler H. T., Menon N. K., Mitchison D. A., Rist N., Smelev N. A. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes. Bull World Health Organ. 1969;41(1):21–43. [PMC free article] [PubMed] [Google Scholar]
  4. Cavalli-Sforza L L, Lederberg J. Isolation of Pre-Adaptive Mutants in Bacteria by Sib Selection. Genetics. 1956 May;41(3):367–381. doi: 10.1093/genetics/41.3.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gálvez-Brandon J., Bartmann K. Statistical aspects of the proportion method for determining the drug-resistance of tubercle bacilli. Scand J Respir Dis. 1969;50(1):1–18. [PubMed] [Google Scholar]
  6. HSIE J. Y., BRYSON V. Genetic studies on the development of resistance to neomycin and dihydrostreptomycin in Myobacterium ranae. Am Rev Tuberc. 1950 Sep;62(3):286–299. doi: 10.1164/art.1950.62.3.286. [DOI] [PubMed] [Google Scholar]
  7. JENSEN K. A., KLAER I. A STUDY ON PROBLEMS OF RESISTANCE. 2. INVESTIGATIONS INTO THE EMERGENCE OF RESISTANCE OF TUBERCLE BACILLI TO ISONIAZID. Acta Pathol Microbiol Scand. 1964;61:427–436. doi: 10.1111/apm.1964.61.3.427. [DOI] [PubMed] [Google Scholar]
  8. LEDERBERG J., LEDERBERG E. M. Replica plating and indirect selection of bacterial mutants. J Bacteriol. 1952 Mar;63(3):399–406. doi: 10.1128/jb.63.3.399-406.1952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Leat J. L., Marks J. Improvement of drg-sensitivity tests on tubercle bacilli. Tubercle. 1970 Mar;51(1):68–75. doi: 10.1016/0041-3879(70)90129-7. [DOI] [PubMed] [Google Scholar]
  10. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MIDDLEBROOK G. Techniques of drug-resistance tests. Am Rev Tuberc. 1954 Nov;70(5):922–923. doi: 10.1164/art.1954.70.5.922. [DOI] [PubMed] [Google Scholar]
  12. SZYBALSKI W., BRYSON V. Bacterial resistance studies with derivatives of isonicotinic acid. Am Rev Tuberc. 1952 Jun;65(6):768–770. [PubMed] [Google Scholar]
  13. Tripathy S. P., Menon N. K., Mitchison D. A., Narayana A. S., Somasundaram P. A., Stott H., Velu S. Response to treatment with isoniazid plus PAS of tuberculous patients with primary isoniazid resistance. Tubercle. 1969 Sep;50(3):257–268. doi: 10.1016/0041-3879(69)90050-6. [DOI] [PubMed] [Google Scholar]
  14. Yegian D., Vanderlinde R. J. A Quantitative Analysis of the Resistance of Mycobacteria to Streptomycin. J Bacteriol. 1948 Aug;56(2):177–186. doi: 10.1128/jb.56.2.177-186.1948. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Applied Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES