1887

Abstract

Mycobacterial α-, methoxy- and keto-mycolic acid methyl esters were separated by argentation chromatography into mycolates with no double bond, with one double bond or with one double bond. Meromycolic acids were prepared from each methyl mycolate fraction by pyrolysis, followed by silver oxide oxidation, and analysed by high-energy collision-induced dissociation/fast atom bombardment MS to reveal the exact locations of the functional groups within the meromycolate chain. The locations of and double bonds, and cyclopropane rings, methoxy and keto groups, and methyl branches within the meromycolate chain were determined from their characteristic fragment ion profiles, and the structures of the meromycolic acids, including those with three functional groups extracted from H37Ra, BCG and , were established. Meromycolic acids with one double bond were structurally closely related to those with one cyclopropane ring, whereas the meromycolic acids with one cyclopropane ring were closely related to the corresponding meromycolic acids with one cyclopropane ring. A close relationship between methoxy- and keto-meromycolic acids was also implied. The relationship between the meromycolic acids with a double bond and the other meromycolic acids was not clearly revealed, and they did not appear to be immediate substrates for cyclopropanation.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-148-6-1881
2002-06-01
2020-09-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/148/6/1481881a.html?itemId=/content/journal/micro/10.1099/00221287-148-6-1881&mimeType=html&fmt=ahah

References

  1. Adams J., Songer M. J. 1993; Charge-remote fragmentations for structural determination of lipids. Trends Anal Chem12:28–35[CrossRef]
    [Google Scholar]
  2. Barry C. E.III, Lee R. E., Mdluli K., Sampson A. E., Schroeder B. G., Slayden R. A. 1998; Mycolic acids: structure, biosynthesis and physiological functions. Prog Lipid Res37:143–179[CrossRef]
    [Google Scholar]
  3. Brennan P. J., Nikaido H. 1995; The envelope of mycobacteria. Annu Rev Biochem64:29–63[CrossRef]
    [Google Scholar]
  4. Chen C., Gross M. L. 2000; Applications and mechanism of charge-remote fragmentation. Mass Spectrom Rev19:398–420[CrossRef]
    [Google Scholar]
  5. Cordero N., Wesdemiotis C. 1994; Characterization of the neutral products formed upon the charge-remote fragmentation of fatty acid ions. Anal Chem66:861–866[CrossRef]
    [Google Scholar]
  6. Crockett J. S., Gross M. L., Christie W. W., Holman R. T. 1990; Collision activation of a series of homoconjugated octadecadienoic acids with fast atom bombardment and tandem mass spectrometry. Am Soc Mass Spectrom1:183–191[CrossRef]
    [Google Scholar]
  7. Danielson S. J., Gray G. R. 1982; Structures of the two homologous series of dialkene mycolic acids from Mycobacterium smegmatis . J Biol Chem257:12196–12203
    [Google Scholar]
  8. Dmitriev B. A., Ehlers S., Rietschel E. T., Brennan P. J. 2000; Molecular mechanics of the mycobacterial cell wall: from horizontal layers to vertical scaffolds. Int J Med Microbiol290:251–258[CrossRef]
    [Google Scholar]
  9. Draper P. 1998; The outer parts of the mycobacterial envelope as permeability barriers. Front Biosci3:1253–1261
    [Google Scholar]
  10. Dubnau E., Lanéelle M. A., Soares S., Benichou A., Vaz T., Prome D., Promé J. C., Daffé M., Quémard A. 1997; Mycobacterium bovis BCG genes involved in the biosynthesis of cyclopropyl keto- and hydroxy-mycolic acids. Mol Microbiol23:313–322[CrossRef]
    [Google Scholar]
  11. Dubnau E., Chan J., Raynoud C., Mohan V. P., Lanéelle M. A., Yu K., Quémard A., Smith I., Daffé M. 2000; Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol Microbiol36:630–637
    [Google Scholar]
  12. Gensler W. J., Marshall J. P. 1977; Structure of mycobacterial bis-cyclopropane mycolates by mass spectometry. Chem Phys Lipids19:128–143[CrossRef]
    [Google Scholar]
  13. George K. M., Yuan Y., Sherman D. R., Barry III C. E. 1995; The biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis . J Biol Chem270:27292–27298[CrossRef]
    [Google Scholar]
  14. Glickman M. S., Cahill S. M., Jacobs W. R. Jr. 2001; The Mycobacterium tuberculosis cmaA2 gene encodes a mycolic acid trans -cyclopropane synthetase. J Biol Chem276:2228–2233[CrossRef]
    [Google Scholar]
  15. Jackson M., Raynaud C., Lanéelle M. A., Guilhot C., Laurent-Winter C., Ensergulix D., Gicquel B., Daffé M. 1999; Inactivation of the antigen 85C gene profoundly affects the mycolate content and alters the permeability of the Mycobacterium tuberculosis cell envelope. Mol Microbiol31:1573–1587[CrossRef]
    [Google Scholar]
  16. Jensen N. J., Tomer K. B., Gross M. L., Wesdemiotis C. 1985; Gas-phase ion decompositions occurring remote to charge site. J Am Chem Soc107:1863–1868[CrossRef]
    [Google Scholar]
  17. Krembel J., Etémadi A. H. 1966; Sur la structure d’un nouveau type d’acides mycoliques de Mycobacterium smegmatis . Tetrahedron22:1113–1119[CrossRef]
    [Google Scholar]
  18. Lederer E. 1969; Some problems concerning biological C-alkylation reaction and phytosterol biosynthesis. Q Rev Chem Soc Lond23:453–481[CrossRef]
    [Google Scholar]
  19. Liu J., Nikaido H. 1999; A mutant of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids accumulates meromycolates. Proc Natl Acad Sci USA96:4011–4016[CrossRef]
    [Google Scholar]
  20. Liu J., Barry III C. E., Besra G. S., Nikaido H. 1996; Mycolic acid structure determines the fluidity of the mycobacterial cell wall. J Biol Chem271:29545–29551[CrossRef]
    [Google Scholar]
  21. McNeil M., Daffé M., Brennan P. J. 1991; Locations of the mycoloyl ester substituents in the cell walls of mycobacteria. J Biol Chem266:13217–13223
    [Google Scholar]
  22. Minnikin D. E., Polgar N. 1967a; The methoxymycolic and ketomycolic acids from human tubercle bacilli. Chem Commun (J Chem Soc Sect D)1172–1174
    [Google Scholar]
  23. Minnikin D. E., Polgar N. 1967b; The mycolic acids from human and avian bacilli. Chem Commun (J Chem Soc Sect D)916–918
    [Google Scholar]
  24. Paul T. R., Beveridge J. 1992; Re-evaluation of envelope profiles and cytoplasmic ultrastructure of mycobacteria processed by conventional embedding and freeze-substitution protocols. J Bacteriol174:6508–6517
    [Google Scholar]
  25. Paul T. R., Beveridge J. 1994; Preservation of surface lipids and determination of ultrastructure of Mycobacterium kansasii by freeze-substitution. Infect Immun62:1542–1555
    [Google Scholar]
  26. Qureshi N., Takayama K., Jordi H. C., Schnoes H. K. 1978; Characterization of the purified components of a new homologous series of alpha-mycolic acids from Mycobacterium tuberculosis H37Ra. J Biol Chem253:5411–5417
    [Google Scholar]
  27. Savagnac A., Aurella H., Casas C., Couderc F., Gavard P., Promé D., Promé J. 1989; Structure determination of mycolic acids by using charge-remote fragmentation. Chem Phys Lipids51:31–38[CrossRef]
    [Google Scholar]
  28. Schroeder B. G., Barry III C. E. 2001; The specificity of methyl transferases involved in trans mycolic acid biosynthesis in Mycobacterium tuberculosis and Mycobacterium smegmatis . Bioorg Chem29:164–177[CrossRef]
    [Google Scholar]
  29. Steenken W. Jr, Gardner L. U. 1946; History of H37 strain of human tubercle bacillus. Am Rev Tuber54:62–66
    [Google Scholar]
  30. Takayama K., Qureshi N., Jordi H. C., Schnoes H. K. 1979; Separation of homologous series of mycolic acids from Mycobacterium tuberculosis H37Ra by high performance liquid chromatography. In Biological/Biochemical Applications of Liquid Chromatography pp91–101 Edited by Hawk G. L.. New York: Marcel Dekker;
    [Google Scholar]
  31. Tomer K. B., Jensen N. J., Gross M. L. 1986; Fast atom bombardment and tandem mass spectrometry for determining structural modification of fatty acids. Anal Chem58:2429–2433[CrossRef]
    [Google Scholar]
  32. Wang L., Slayden R. A., Barry III C. E., Liu J. 2000; Cell wall structure of a mutant of Mycobacterium smegmatis defective in the biosynthesis of mycolic acids. J Biol Chem275:7224–7229[CrossRef]
    [Google Scholar]
  33. Watanabe M., Aoyagi Y., Ridell M., Minnikin D. E. 2001; Separation and characterization of individual mycolic acids in representative mycobacteria. Microbiology147:1825–1837
    [Google Scholar]
  34. Yuan Y., Lee R. E., Besra G. S., Belisle J. T., Barry III C. E. 1995; Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis . Proc Natl Acad Sci USA92:6630–6634[CrossRef]
    [Google Scholar]
  35. Yuan Y., Zhu Y. Q., Crane D. D., Barry III C. E. 1998; The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis . Mol Microbiol29:1449–1458[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-148-6-1881
Loading
/content/journal/micro/10.1099/00221287-148-6-1881
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error