1887

Abstract

The structure of cord factor was studied in several strains of , including ‘’ TMC 5135, considered as highly immunogenic in experimental tuberculosis and leprosy. The mycolic acids liberated from cord factor were identified in all cases as ′-, - and keto-mycolates. According to the general NMR and MS data, ′-mycolates were mono-unsaturated and contained from 64 to 68 carbon atoms, whereas -mycolates mainly presented two 2,3-disubstituted cyclopropane rings and a chain length of 80–91 carbon atoms; keto-mycolates mostly contained one cyclopropane ring and 85–91 carbon atoms. Taking into account the H-NMR results, strains varied in the ratio of the different mycolates, and the high levels of keto-mycolates found in the cord factors of TMC 5135 and ATCC 25275 stood out. Notably, MS revealed that the odd carbon number series of -mycolates (C87–C89) predominated in the cord factor of TMC 5135, in contrast to the remaining studied strains, in which the even (C84–C86) and odd carbon number series appeared more equal. The fine structural differences detected among the cord factors studied did not seem to be relevant to the general capacity of these molecules to induce the secretion of tumour necrosis factor alpha, as the cord factors from several strains of (TMC 5135, IPK-342 and ATCC 25275) induced similar amounts of this cytokine in RAW 264.7 cells.

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2010-12-01
2019-10-20
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References

  1. Bhatt, A., Fujiwara, N., Bhatt, K., Gurcha, S. S., Kremer, L., Cheng, B., Chan, J., Porcelli, S. A., Kobayashi, K. & other authors ( 2007; ). Deletion of kasB in Mycobacterium tuberculosis causes loss of acid-fastness and subclinical latent tuberculosis in immunocompetent mice. Proc Natl Acad Sci U S A 104, 5157–5162.[CrossRef]
    [Google Scholar]
  2. Bloch, H. ( 1950; ). Studies on the virulence of tubercle bacilli. Isolation and biological properties of a constituent of virulent organisms. J Exp Med 91, 197–218.[CrossRef]
    [Google Scholar]
  3. Bowdish, D. M. E., Sakamoto, K., Kim, M.-J., Mariliis Kroos, M., Mukhopadhyay, S., Leifer, C. A., Tryggvason, K., Gordon, S. & Russell, D. G. ( 2009; ). MARCO, TLR2, and CD14 are required for macrophage cytokine responses to mycobacterial trehalose dimycolate and Mycobacterium tuberculosis. PLoS Pathog 5, e1000474.[CrossRef]
    [Google Scholar]
  4. Brennan, P. J. & Nikaido, H. ( 1995; ). The envelope of mycobacteria. Annu Rev Biochem 64, 29–63.[CrossRef]
    [Google Scholar]
  5. Cooper, A. M. ( 2009; ). Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27, 393–422.[CrossRef]
    [Google Scholar]
  6. Daffé, M. & Draper, P. ( 1998; ). The envelope layers of mycobacteria with reference to their pathogenicity. Adv Microb Physiol 39, 131–203.
    [Google Scholar]
  7. Dao, D. N., Sweeney, K., Hsu, T., Gurcha, S. S., Nascimento, I. P., Roshevsky, D., Besra, G., Chan, J., Porcelli, S. A. & Jacobs, W. R., Jr ( 2008; ). Mycolic acid modification by mmaA4 gene of M. tuberculosis modulates IL-12 production. PLoS Pathog 4, e1000081.[CrossRef]
    [Google Scholar]
  8. Dietrich, J. & Doherty, T. M. ( 2009; ). Interaction of Mycobacterium tuberculosis with the host: consequences for vaccine development. APMIS 117, 440–457.[CrossRef]
    [Google Scholar]
  9. Divya Jyothi, M., Garg, S. K. & Singh, N. B. ( 2000; ). Mechanisms involved in protective immune response generated by secretory proteins of Mycobacterium habana against experimental tuberculosis. Scand J Immunol 51, 502–510.[CrossRef]
    [Google Scholar]
  10. Dubnau, E., Chan, J., Raynaud, C., Mohan, V. P., Laneélle, M. A., Yu, K., Quémard, A., Smith, I. & Daffé, M. ( 2000; ). Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol Microbiol 36, 630–637.
    [Google Scholar]
  11. Falkinham, J. O., III ( 1996; ). Epidemiology of infection by nontuberculous mycobacteria. Clin Microbiol Rev 9, 177–215.
    [Google Scholar]
  12. Fujita, Y., Naka, T., McNeil, M. R. & Yano, I. ( 2005; ). Intact molecular characterization of cord factor (trehalose 6,6′-dimycolate) from nine species of mycobacteria by MALDI-TOF mass spectrometry. Microbiology 151, 3403–3416.[CrossRef]
    [Google Scholar]
  13. Fujita, Y., Okamoto, Y., Uenishi, Y., Sunagawa, M., Uchiyama, T. & Yano, I. ( 2007; ). Molecular and supramolecular structure related differences in toxicity and granulomatogenic activity of mycobacterial cord factor in mice. Microb Pathog 43, 10–21.[CrossRef]
    [Google Scholar]
  14. Glickman, M. S., Cox, J. S. & Jacobs, W. R., Jr ( 2000; ). A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol Cell 5, 717–727.[CrossRef]
    [Google Scholar]
  15. Gupta, H. P., Singh, N. B., Mathur, I. S. & Gupta, S. K. ( 1979; ). Mycobacterium habana, a new immunogenic strain in experimental tuberculosis. Indian J Exp Biol 17, 1190–1193.
    [Google Scholar]
  16. Hayashi, D., Takii, T., Fujiwara, N., Fujita, Y., Yano, I., Yamamoto, S., Kondo, M., Inagaki, M., Yasuda, E. & other authors ( 2009; ). Comparable studies of immunostimulating activities in vitro among Mycobacterium bovis Bacillus Calmette-Guérin (BCG) substrains. FEMS Immunol Med Microbiol 56, 116–128.[CrossRef]
    [Google Scholar]
  17. Hunter, R. L., Olsen, M. R., Jagannath, C. & Actor, J. K. ( 2006; ). Multiple roles of cord factor in the pathogenesis of primary, secondary, and cavitary tuberculosis, including a revised description of the pathology of secondary disease. Ann Clin Lab Sci 36, 371–386.
    [Google Scholar]
  18. Hunter, R. L., Armitige, L., Jagannath, C. & Actor, J. K. ( 2009; ). TB research at UT-Houston. A review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis. Tuberculosis (Edinb) 89, S18–S25.[CrossRef]
    [Google Scholar]
  19. Ishikawa, E., Ishikawa, T., Morita, Y. S., Toyonaga, K., Yamada, H., Takeuchi, O., Kinoshita, T., Akira, S., Yoshikai, Y. & Yamashaki, S. ( 2009; ). Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J Exp Med 206, 2879–2888.[CrossRef]
    [Google Scholar]
  20. Khoo, K. H., Chaterjee, D., Dell, A., Morris, H. R., Brennan, P. J. & Draper, P. ( 1996; ). Novel O-methylated terminal glucuronic acid characterizes the polar glycopeptidolipids of Mycobacterium habana TMC 5135. J Biol Chem 271, 12333–12342.[CrossRef]
    [Google Scholar]
  21. Lin, F. L., van Halbeek, H. & Bertozzi, C. R. ( 2007; ). Synthesis of mono- and dideoxygenated α,α-trehalose analogs. Carbohydr Res 342, 2014–2030.[CrossRef]
    [Google Scholar]
  22. McNeil, M., Daffé, M. & Brennan, P. J. ( 1991; ). Location of mycoloyl ester substituents in the cell walls of mycobacteria. J Biol Chem 266, 13217–13223.
    [Google Scholar]
  23. Mederos, L. M., Gutiérrez, A. M. & Valdivia, J. A. ( 1992; ). Utilization of a new culture medium in biochemical tests for the mycobacterial classification. Mem Inst Oswaldo Cruz 87, 441.[CrossRef]
    [Google Scholar]
  24. Mederos, L. M., Valdivia, J. A. & Valero-Guillén, P. L. ( 1998; ). Analysis of lipids reveals differences between ‘Mycobacterium habana’ and Mycobacterium simiae. Microbiology 144, 1181–1188.[CrossRef]
    [Google Scholar]
  25. Mederos, L. M., Valdivia, J. A. & Valero-Guillén, P. L. ( 2006; ). Lipids of ‘Mycobacterium habana’, a synonym of Mycobacterium simiae with vaccine potential. Tuberculosis (Edinb) 86, 324–329.[CrossRef]
    [Google Scholar]
  26. Mederos, L., Valdivia, J. A. & Valero-Guillén, P. L. ( 2007; ). Analysis of the structure of mycolic acids of Mycobacterium simiae reveals a particular composition of α-mycolates in strain ‘habana’ TMC 5135, considered as immunogenic in tuberculosis and leprosy. Microbiology 153, 4159–4165.[CrossRef]
    [Google Scholar]
  27. Mederos, L., Valdivia, J. A. & Valero-Guillén, P. L. ( 2008; ). New variants of polar glycopeptidolipids detected in Mycobacterium simiae, including ‘habana’ strains, as evidenced by electrospray ionization-ion trap-mass spectrometry. J Appl Microbiol 105, 602–614.[CrossRef]
    [Google Scholar]
  28. Minnikin, D. E. ( 1982; ). Lipids: complex lipids. In The Biology of the Mycobacteria, vol. 1, pp. 95–184. Edited by Ratledge, C. & Stanford, J. L.. London. : Academic Press.
    [Google Scholar]
  29. Minnikin, D. E. & Goodfellow, M. ( 1976; ). Lipid composition in the classification and identification of nocardiae and related taxa. In The Biology of the Nocardiae, pp. 160–219. Edited by Goodfellow, M., Brownell, G. H. & Serrano, J. A.. London. : Academic Press.
    [Google Scholar]
  30. Niescher, S., Wray, V., Lang, S., Kaschabek, S. R. & Schlömann, M. ( 2006; ). Identification and structural characterisation of novel trehalose dinocardomycolates from n-alkane-grown Rhodococcus opacus 1CP. Appl Microbiol Biotechnol 70, 605–611.[CrossRef]
    [Google Scholar]
  31. Nishizawa, M., Yamamoto, H., Imagawa, H., Barbier-Chassafière, V., Petit, M., Azuma, I. & Papy-García, D. ( 2007; ). Efficient synthesis of a series of trehalose dimycolate (TDM)/trehalose dicorynemycolate (TDCM) analogues and their interleukin-6 level enhancement activity in mice sera. J Org Chem 72, 1627–1633.[CrossRef]
    [Google Scholar]
  32. Noll, H., Bloch, H., Asselineau, J. & Lederer, E. ( 1956; ). The chemical structure of the cord factor of Mycobacterium tuberculosis. Biochim Biophys Acta 20, 299–309.[CrossRef]
    [Google Scholar]
  33. Ozeki, Y., Tsutsui, H., Kawada, N., Suzuki, H., Kataoka, M., Kodama, T., Yano, I., Kaneda, K. & Kobayashi, K. ( 2006; ). Macrophage scavenger receptor down-regulates mycobacterial cord factor-induced proinflammatory cytokine production by alveolar and hepatic macrophages. Microb Pathog 40, 171–176.[CrossRef]
    [Google Scholar]
  34. Quémard, A., Lanéelle, M. A., Marrackhi, H., Promé, D., Dubnau, E. & Daffé, M. ( 1997; ). Structure of a hydroxymycolic acid potentially involved in the synthesis of oxygenated mycolic acids of Mycobacterium tuberculosis complex. Eur J Biochem 250, 758–763.[CrossRef]
    [Google Scholar]
  35. Rao, V., Fujiwara, N., Porcelli, S. A. & Glickman, M. S. ( 2005; ). Mycobacterium tuberculosis controls host innate immune activation through cyclopropane modification of a glycolipid effector molecule. J Exp Med 201, 535–543.[CrossRef]
    [Google Scholar]
  36. Rao, V., Gao, F., Chen, B., Jacobs, W. R., Jr & Glickman, M. S. ( 2006; ). Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence. J Clin Invest 116, 1660–1667.[CrossRef]
    [Google Scholar]
  37. Rhoades, E., Hsu, F. F., Torrelles, J. B., Turk, J., Chaterjee, D. & Russell, D. G. ( 2003; ). Identification and macrophage-activating activity of glycolipids released from intracellular Mycobacterium bovis BCG. Mol Microbiol 48, 875–888.[CrossRef]
    [Google Scholar]
  38. Riley, L. W. ( 2006; ). Of mice, men, and elephants: Mycobacterium tuberculosis cell envelope and pathogenesis. J Clin Invest 116, 1475–1478.[CrossRef]
    [Google Scholar]
  39. Schroeder, B. G. & Barry, C. E. ( 2001; ). The specificity of methyl transferases involved in trans mycolic acid biosynthesis in Mycobacterium tuberculosis and Mycobacterium smegmatis. Bioorg Chem 29, 164–177.[CrossRef]
    [Google Scholar]
  40. Silva, C. L., Tincani, I., Brandao-Filho, S. L. & Faccioli, L. H. ( 1988; ). Mouse cachexia induced by trehalose dimycolate from Nocardia asteroides. J Gen Microbiol 134, 1629–1633.
    [Google Scholar]
  41. Singh, N. B., Lowe, C. R. E., Rees, R. J. W. & Colston, M. J. ( 1989; ). Vaccination of mice against Mycobacterium leprae infection. Infect Immun 57, 653–655.
    [Google Scholar]
  42. Singh, N. B., Gupta, H. P., Srivastava, A., Kandpal, H. & Srivastava, U. M. ( 1997; ). Lymphostimulatory and delayed-type hypersensitivity responses to a candidate leprosy vaccine strain: Mycobacterium habana. Lepr Rev 68, 125–130.
    [Google Scholar]
  43. Takayama, K., Wang, C. & Besra, G. S. ( 2005; ). Pathway to synthesis and processing of mycolic acids in Mycobacterium tuberculosis. Clin Microbiol Rev 18, 81–101.[CrossRef]
    [Google Scholar]
  44. Takimoto, H., Maruyama, H., Shimada, K.-L., Yakabe, R., Yano, I. & Kumazawa, Y. ( 2006; ). Interferon-γ independent formation of pulmonary granuloma in mice by injections with trehalose dimycolate (cord factor), lipoarabinomannan and phosphatidylinositol mannosides isolated from Mycobacterium tuberculosis. Clin Exp Immunol 144, 134–141.[CrossRef]
    [Google Scholar]
  45. Ueda, S., Fujiwara, N., Naka, T., Sakaguchi, I., Ozeki, Y., Yano, I., Kasama, T. & Kobayashi, K. ( 2001; ). Structure-activity relationship of mycoloyl glycolipids derived from Rhodococcus sp. 4306. Microb Pathog 30, 91–99.[CrossRef]
    [Google Scholar]
  46. Valdivia, J. A. ( 1973; ). Mycobacterium habana: clinical and epidemiological significance. Ann Soc Belg Med Trop 53, 263–266.
    [Google Scholar]
  47. Villeneuve, M., Kawai, M., Watanabe, M., Aoyagi, I., Hitotsuyanagi, Y., Takeya, K., Gouda, H., Hirono, S., Minnikin, D. E. & Nakahara, H. ( 2007; ). Conformational behavior of oxygenated mycobacterial mycolic acids from Mycobacterium bovis BCG. Biochim Biophys Acta 1768, 1717–1726.[CrossRef]
    [Google Scholar]
  48. Villeneuve, M., Kawai, M., Watanabe, M., Aoyagi, I., Hitotsuyanagi, Y., Takeya, K., Gouda, H., Hirono, S., Minnikin, D. E. & Nakahara, H. ( 2010; ). Differential conformational behaviors of α-mycolic acids in Langmuir monolayers and computer simulation. Chem Phys Lipids 163, 569–579.[CrossRef]
    [Google Scholar]
  49. Watanabe, M., Ohta, A., Sasaki, A. & Minnikin, D. E. ( 1999; ). Structure of a new glycolipid from the Mycobacterium avium–Mycobacterium intracellulare complex. J Bacteriol 181, 2293–2297.
    [Google Scholar]
  50. Watanabe, M., Aoyagi, Y., Ridell, M. & Minnikin, D. E. ( 2001; ). Separation and characterization of individual mycolic acids in representative mycobacteria. Microbiology 147, 1825–1837.
    [Google Scholar]
  51. Watanabe, M., Aoyagi, Y., Mitome, H., Fujita, T., Naoki, H., Ridell, M. & Minnikin, D. E. ( 2002; ). Location of functional groups in mycobacterial meromycolate chains; the recognition of new structural principles in mycolic acids. Microbiology 148, 1881–1902.
    [Google Scholar]
  52. Weiszfeiler, J. G. & Karczag, E. ( 1976; ). Synonymy of Mycobacterium simiae Karasseva et al. 1965 and Mycobacterium habana Valdivia et al. 1971. Int J Syst Bacteriol 26, 474–477.[CrossRef]
    [Google Scholar]
  53. Welsh, K. J., Abbott, A. N., Hwang, S.-A., Indrigo, J., Armitige, L. Y., Blackburn, M. R., Hunter, R. L., Jr & Actor, J. K. ( 2008; ). A role for tumour necrosis factor-α, complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,6′-dimycolate induced granulomatous response. Microbiology 154, 1813–1824.[CrossRef]
    [Google Scholar]
  54. Werninghaus, K., Babiak, A., Groß, O., Hölscher, C., Dietrich, H., Agger, E. M., Mages, J., Mocsai, A., Schoenen, H. & other authors ( 2009; ). Adjuvanticity of a synthetic cord factor analogue for subunit Mycobacterium tuberculosis vaccination requires FcRγ-Syk-Card9-dependent innate immune activation. J Exp Med 206, 89–97.[CrossRef]
    [Google Scholar]
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