Skip to main content
PMC home page
Applied Microbiology logoLink to Applied Microbiology
. 1971 May;21(5):888–892. doi: 10.1128/am.21.5.888-892.1971

Resistance to d-Cycloserine in the Tubercle Bacilli: Mutation Rate and Transport of Alanine in Parental Cells and Drug-Resistant Mutants

Hugo L David 1
PMCID: PMC377303  PMID: 4995732

Abstract

A single transport system was found to accumulate l- and d-alanine, glycine and d-serine in Mycobacterium tuberculosis. The results of inhibition experiments suggested that the antibiotics d-cycloserine and O-carbamyl-d-serine were also transported by the alanine-glycine-d-serine system. A d-cycloserine-resistant permease-competent (d-CSr/perm+) mutant and a d-cycloserine-resistant permease-defective (d-CSr/perm−) mutant were isolated. The d-CSr/perm− mutant was not found to be more resistant to the drug than was the d-CSr/perm+ mutant. The data were consistent with the conclusion that resistance to d-cycloserine in the tubercle bacilli is primarily due to mutations in the gene(s) controlling the enzyme d-alanyl-d-alanine synthetase. The mutation rate was calculated to be about 10−10 mutations per bacterium per generation.

Full text

PDF
890

Selected References

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

  1. Curtiss R., 3rd, Charamella L. J., Berg C. M., Harris P. E. Kinetic and genetic analyses of D-cycloserine inhibition and resistance in Escherichia coli. J Bacteriol. 1965 Nov;90(5):1238–1250. doi: 10.1128/jb.90.5.1238-1250.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. David H. L. Effect of O-carbamyl-D-serine on the growth of mycobacterium tuberculosis. Am Rev Respir Dis. 1970 Jul;102(1):68–74. doi: 10.1164/arrd.1970.102.1.68. [DOI] [PubMed] [Google Scholar]
  3. David H. L. Probability distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl Microbiol. 1970 Nov;20(5):810–814. doi: 10.1128/am.20.5.810-814.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. David H. L., Takayama K., Goldman D. S. Susceptibility of mycobacterial D-alanyl-D-alanine synthetase to D-cycloserine. Am Rev Respir Dis. 1969 Oct;100(4):579–581. doi: 10.1164/arrd.1969.100.4.579. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Reitz R. H., Slade H. D., Neuhaus F. C. The biochemical mechanisms of resistance by streptococci to the antibiotics D-cycloserine and O-carbamyl-D-serine. Biochemistry. 1967 Aug;6(8):2561–2570. doi: 10.1021/bi00860a038. [DOI] [PubMed] [Google Scholar]
  7. TANAKA N., UMEZAWA H. SYNERGISM OF D-4-AMINO-3-ISOXAZOLIDONE AND O-CARBAMYL-D-SERINE. J Antibiot (Tokyo) 1964 Jan;17:8–10. [PubMed] [Google Scholar]
  8. TSUKAMURA M., NODA Y., HAYASHI M., YAMAMOTO M. A genetic study on the cycloserine-resistance of Mycobacterium tuberculosis var. hominis. Jpn J Microbiol. 1959 Jan;3:1–8. doi: 10.1111/j.1348-0421.1959.tb00095.x. [DOI] [PubMed] [Google Scholar]
  9. Wargel R. J., Shadur C. A., Neuhaus F. C. Mechanism of D-cycloserine action: transport systems for D-alanine, D-cycloserine, L-alanine, and glycine. J Bacteriol. 1970 Sep;103(3):778–788. doi: 10.1128/jb.103.3.778-788.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Yabu K. Amino acid transport in Mycobacterium smegmatis. J Bacteriol. 1970 Apr;102(1):6–13. doi: 10.1128/jb.102.1.6-13.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES