Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1993 Jun;61(6):2296–2303. doi: 10.1128/iai.61.6.2296-2303.1993

Development of a trehalose 6,6'-dimycolate model which explains cord formation by Mycobacterium tuberculosis.

C A Behling 1, B Bennett 1, K Takayama 1, R L Hunter 1
PMCID: PMC280848  PMID: 8500871

Abstract

Trehalose 6,6'-dimycolate (TDM) is a glycolipid of mycobacteria that displays an unusual toxicity and has been reported to be a virulence factor for Mycobacterium tuberculosis. Lack of understanding of the toxicity has impeded acceptance of TDM as a virulence factor. We previously reported that the toxicity of TDM depends on its presentation as a surface monolayer consisting of 30% trehalose and 70% exposed mycolic acid moieties. This paper further investigates the structure of the TDM monolayer. It began with the observation that beads coated with TDM, but not with closely related analogs, aggregate to form organized structures resembling the cords of virulent mycobacteria. This implied that the TDM molecules in the monolayer were arranged in an organized structure. This structure was investigated by real-time kinetic microscopy, scanning electron microscopy, and gross observations of the adhesion patterns of TDM-coated beads. In each of these models, the structures induced by TDM differed from those of analogs or other amphiphiles studied. These observations were used to construct a model of the structure of TDM monolayer which envisions linear arrays of TDM molecules arranged in a circumferential pattern on beads with discontinuities only at the two poles.

Full text

PDF
2296

Images in this article

2298Image
on p.2298
2298Image
on p.2298
2299Image
on p.2299
2300Image
on p.2300
2301Image
on p.2301

Selected References

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

  1. BLOCH H., NOLL H. Studies on the virulence of Tubercle bacilli; the effect of cord factor on murine tuberculosis. Br J Exp Pathol. 1955 Feb;36(1):8–17. [PMC free article] [PubMed] [Google Scholar]
  2. BLOCH H., NOLL H. Studies on the virulence of tubercle bacilli; variations in virulence effected by tween 80 and thiosemicarbazone. J Exp Med. 1953 Jan;97(1):1–16. doi: 10.1084/jem.97.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BLOCH H. Studies on the virulence of tubercle bacilli; isolation and biological properties of a constituent of virulent organisms. J Exp Med. 1950 Feb;91(2):197-218, pl. doi: 10.1084/jem.91.2.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Lemaire G., Tenu J. P., Petit J. F., Lederer E. Natural and synthetic trehalose diesters as immunomodulators. Med Res Rev. 1986 Jul-Sep;6(3):243–274. doi: 10.1002/med.2610060302. [DOI] [PubMed] [Google Scholar]
  5. NOLL H., BLOCH H., ASSELINEAU J., LEDERER E. The chemical structure of the cord factor of Mycobacterium tuberculosis. Biochim Biophys Acta. 1956 May;20(2):299–309. doi: 10.1016/0006-3002(56)90289-x. [DOI] [PubMed] [Google Scholar]
  6. Quinn P. J., Koynova R. D., Lis L. J., Tenchov B. G. Lamellar gel-lamellar liquid crystal phase transition of dipalmitoylphosphatidylcholine multilayers freeze-dried from aqueous trehalose solutions. A real-time X-ray diffraction study. Biochim Biophys Acta. 1988 Jul 21;942(2):315–323. doi: 10.1016/0005-2736(88)90033-8. [DOI] [PubMed] [Google Scholar]
  7. Retzinger G. S., Meredith S. C., Hunter R. L., Takayama K., Kézdy F. J. Identification of the physiologically active state of the mycobacterial glycolipid trehalose 6,6'-dimycolate and the role of fibrinogen in the biologic activities of trehalose 6,6'-dimycolate monolayers. J Immunol. 1982 Aug;129(2):735–744. [PubMed] [Google Scholar]
  8. Retzinger G. S., Meredith S. C., Takayama K., Hunter R. L., Kézdy F. J. The role of surface in the biological activities of trehalose 6,6'-dimycolate. Surface properties and development of a model system. J Biol Chem. 1981 Aug 10;256(15):8208–8216. [PubMed] [Google Scholar]
  9. Saito R., Tanaka A., Sugiyama K., Azuma I., Yamamura Y. Adjuvant effect of cord factor, a mycobacterial lipid. Infect Immun. 1976 Mar;13(3):776–781. doi: 10.1128/iai.13.3.776-781.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Silva C. L., Ekizlerian S. M., Fazioli R. A. Role of cord factor in the modulation of infection caused by mycobacteria. Am J Pathol. 1985 Feb;118(2):238–247. [PMC free article] [PubMed] [Google Scholar]
  11. Vosika G., Giddings C., Gray G. R. Phase I study of intravenous mycobacterial cell wall skeleton and trehalose dimycolate attached to oil droplets. J Biol Response Mod. 1984 Dec;3(6):620–626. [PubMed] [Google Scholar]
  12. Yarkoni E., Rapp H. J. Influence of oil and Tween concentrations on enhanced endotoxin lethality in mice pretreated with emulsified trehalose-6,6'-dimycolate (cord factor). Infect Immun. 1979 May;24(2):571–572. doi: 10.1128/iai.24.2.571-572.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES