Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Jul;37(7):1536–1538. doi: 10.1128/aac.37.7.1536

Ethambutol inhibition of glucose metabolism in mycobacteria: a possible target of the drug.

G Silve 1, P Valero-Guillen 1, A Quemard 1, M A Dupont 1, M Daffe 1, G Laneelle 1
PMCID: PMC188008  PMID: 8363387

Abstract

The addition of D-arabinose, D-galactose, D-glucosamine, or D-mannose to the growth medium of Mycobacterium smegmatis suppressed the inhibitory effects of ethambutol both on acetate labeling of cell wall-linked mycolic acids and on the increase in the delipidated cell dry weight. The addition of D-glucose or D-fructose had no effect. It is proposed that ethambutol inhibits an early step of glucose conversion into the monosaccharides used for the biosynthesis of structurally and biologically important cell wall polysaccharides: arabinogalactan, arabinomannan, and peptidoglycan.

Full text

PDF
1536

Images in this article

Selected References

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

  1. Daffé M., Lanéelle M. A., Roussel J., Asselineau C. Lipides spécifiques de Mycobacterium ulcerans. Ann Microbiol (Paris) 1984 Mar-Apr;135A(2):191–201. [PubMed] [Google Scholar]
  2. Doster B., Murray F. J., Newman R., Woolpert S. F. Ethambutol in the initial treatment of pulmonary tuberculosis. U.S. Public Health Service tuberculosis therapy trials. Am Rev Respir Dis. 1973 Feb;107(2):177–190. doi: 10.1164/arrd.1973.107.2.177. [DOI] [PubMed] [Google Scholar]
  3. Heifets L. B., Iseman M. D., Lindholm-Levy P. J. Ethambutol MICs and MBCs for Mycobacterium avium complex and Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1986 Dec;30(6):927–932. doi: 10.1128/aac.30.6.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hoffner S. E., Svenson S. B., Källenius G. Synergistic effects of antimycobacterial drug combinations on Mycobacterium avium complex determined radiometrically in liquid medium. Eur J Clin Microbiol. 1987 Oct;6(5):530–535. doi: 10.1007/BF02014241. [DOI] [PubMed] [Google Scholar]
  5. Hunter S. W., Gaylord H., Brennan P. J. Structure and antigenicity of the phosphorylated lipopolysaccharide antigens from the leprosy and tubercle bacilli. J Biol Chem. 1986 Sep 15;261(26):12345–12351. [PubMed] [Google Scholar]
  6. 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]
  7. Lacave C., Lanéelle M. A., Daffé M., Montrozier H., Rols M. P., Asselineau C. Etude structurale et métabolique des acides mycoliques de Mycobacterium fortuitum. Eur J Biochem. 1987 Mar 2;163(2):369–378. doi: 10.1111/j.1432-1033.1987.tb10809.x. [DOI] [PubMed] [Google Scholar]
  8. Lacave C., Lanéelle M. A., Lanéelle G. Mycolic acid synthesis by Mycobacterium aurum cell-free extracts. Biochim Biophys Acta. 1990 Feb 23;1042(3):315–323. doi: 10.1016/0005-2760(90)90159-u. [DOI] [PubMed] [Google Scholar]
  9. Lacave C., Quémard A., Lanéelle G. Cell-free synthesis of mycolic acids in Mycobacterium aurum: radioactivity distribution in newly synthesized acids and presence of cell wall in the system. Biochim Biophys Acta. 1990 Jun 28;1045(1):58–68. doi: 10.1016/0005-2760(90)90203-a. [DOI] [PubMed] [Google Scholar]
  10. Quémard A., Lacave C., Lanéelle G. Isoniazid inhibition of mycolic acid synthesis by cell extracts of sensitive and resistant strains of Mycobacterium aurum. Antimicrob Agents Chemother. 1991 Jun;35(6):1035–1039. doi: 10.1128/aac.35.6.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rastogi N., Goh K. S., David H. L. Enhancement of drug susceptibility of Mycobacterium avium by inhibitors of cell envelope synthesis. Antimicrob Agents Chemother. 1990 May;34(5):759–764. doi: 10.1128/aac.34.5.759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Takayama K., Kilburn J. O. Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis. Antimicrob Agents Chemother. 1989 Sep;33(9):1493–1499. doi: 10.1128/aac.33.9.1493. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES