Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1989 Sep;33(9):1493–1499. doi: 10.1128/aac.33.9.1493

Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis.

K Takayama 1, J O Kilburn 1
PMCID: PMC172689  PMID: 2817850

Abstract

Ethambutol at 3.0 micrograms/ml inhibited the transfer of label from D-[14C]glucose into the D-arabinose residue of arabinogalactan in whole cells of a drug-susceptible strain of Mycobacterium smegmatis. This inhibition began almost immediately after exposure of the cells to the drug. When drug-resistant M. smegmatis was used in a similar experiment, no such drug inhibition was detected. A much higher concentration of ethambutol (greater than 50 micrograms/ml) was required to show this inhibition. The drug also inhibited synthesis of arabinose-containing oligosaccharides when a cell-free enzyme system was used. These results suggest that the site of action of ethambutol is somewhere on the pathway between the conversion of D-glucose to D-arabinose and the transfer of arabinose into arabinogalactan. The primary mode of action of ethambutol appears to be inhibition of arabinogalactan synthesis.

Full text

PDF
1493

Selected References

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

  1. AZUMA I., YAMAMURA Y. Studies on the firmly bound lipids of human tubercle bacillus. J Biochem. 1963 Apr;53:275–281. [PubMed] [Google Scholar]
  2. Alpenfels W. F. A rapid and sensitive method for the determination of monosaccharides as their dansyl hydrazones by high-performance liquid chromatography. Anal Biochem. 1981 Jun;114(1):153–157. doi: 10.1016/0003-2697(81)90466-8. [DOI] [PubMed] [Google Scholar]
  3. Beggs W. H., Andrews F. A. Nonspecific ionic inhibition of ethambutol binding by Mycobacterium smegmatis. Antimicrob Agents Chemother. 1973 Aug;4(2):115–119. doi: 10.1128/aac.4.2.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. FORBES M., KUCK N. A., PEETS E. A. EFFECT OF ETHAMBUTOL ON NUCLEIC ACID METABOLISM IN MYCOBACTERIUM SMEGMATIS AND ITS REVERSAL BY POLYAMINES AND DIVALENT CATIONS. J Bacteriol. 1965 May;89:1299–1305. doi: 10.1128/jb.89.5.1299-1305.1965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. FORBES M., KUCK N. A., PEETS E. A. Mode of action of ethambutol. J Bacteriol. 1962 Nov;84:1099–1103. doi: 10.1128/jb.84.5.1099-1103.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kanther R. Myambutol: chemistry, pharmacology, and toxicology. Antibiot Chemother. 1970;16:203–214. doi: 10.1159/000386822. [DOI] [PubMed] [Google Scholar]
  7. Kilburn J. O., Greenberg J. Effect of ethambutol on the viable cell count in Mycobacterium smegmatis. Antimicrob Agents Chemother. 1977 Mar;11(3):534–540. doi: 10.1128/aac.11.3.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kilburn J. O., Takayama K., Armstrong E. L., Greenberg J. Effects of ethambutol on phospholipid metabolism in Mycobacterium smegmatis. Antimicrob Agents Chemother. 1981 Feb;19(2):346–348. doi: 10.1128/aac.19.2.346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kilburn J. O., Takayama K. Effects of ethambutol on accumulation and secretion of trehalose mycolates and free mycolic acid in Mycobacterium smegmatis. Antimicrob Agents Chemother. 1981 Sep;20(3):401–404. doi: 10.1128/aac.20.3.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Misaki A., Ikawa N., Kotani S., Kato T. Cell wall arabinogalactan of Mycobacterium phlei. Biochim Biophys Acta. 1970 Aug 14;215(2):405–408. doi: 10.1016/0304-4165(70)90040-1. [DOI] [PubMed] [Google Scholar]
  11. Misaki A., Yukawa S. Studies on cell walls of Mycobacteria. II. Constitution of polysaccharides from BCG cell walls. J Biochem. 1966 May;59(5):511–520. doi: 10.1093/oxfordjournals.jbchem.a128335. [DOI] [PubMed] [Google Scholar]
  12. THOMAS J. P., BAUGHN C. O., WILKINSON R. G., SHEPHERD R. G. A new synthetic compound with antituberculous activity in mice: ethambutol (dextro-2,2'-(ethylenediimino)-di-l-butanol). Am Rev Respir Dis. 1961 Jun;83:891–893. doi: 10.1164/arrd.1961.83.6.891. [DOI] [PubMed] [Google Scholar]
  13. Takayama K., Armstrong E. L., Kunugi K. A., Kilburn J. O. Inhibition by ethambutol of mycolic acid transfer into the cell wall of Mycobacterium smegmatis. Antimicrob Agents Chemother. 1979 Aug;16(2):240–242. doi: 10.1128/aac.16.2.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Takayama K., Schnoes H. K., Armstrong E. L., Boyle R. W. Site of inhibitory action of isoniazid in the synthesis of mycolic acids in Mycobacterium tuberculosis. J Lipid Res. 1975 Jul;16(4):308–317. [PubMed] [Google Scholar]
  15. Wilson T. M. Clinical experience with ethambutol. Antibiot Chemother. 1970;16:222–229. doi: 10.1159/000386824. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES