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Cord factor (alpha,alpha-trehalose 6,6'-dimycolate) inhibits fusion between phospholipid vesicles
B J Spargo1, L M Crowe, T Ioneda
1Department of Zoology, University of California, Davis 95616.
Abstract:
The persistence of numerous pathogenic bacteria important in disease states, such as tuberculosis, in humans and domestic animals has been ascribed to an inhibition of fusion between the phagosomal vesicles containing the bacteria and lysosomes in the host cells [Elsbach, P. & Weiss, J. (1988) Biochim. Biophys. Acta 974, 29-52; Thoen, C. O. (1988) J. Am. Vet. Med. Assoc. 193, 1045-1048]. In tuberculosis this effect has been indirectly attributed to the production of cord factor (alpha,alpha-trehalose 6,6'-dimycolate). We show here that cord factor is extraordinarily effective at inhibiting Ca2(+)-induced fusion between phospholipid vesicles and suggest a mechanism by which cord factor confers this effect. These findings are likely to be important in our understanding of the pathogenesis and treatment of many diseases of bacterial etiology.
Insights
Cord factor, a component of pathogenic bacteria like tuberculosis, inhibits essential host cell processes. This study demonstrates cord factor
Area of Science:
- Microbiology
- Cell Biology
- Biochemistry
Background:
- Pathogenic bacteria, including Mycobacterium tuberculosis, persist in host cells by evading immune responses.
- Inhibition of phagosome-lysosome fusion is a key mechanism for bacterial survival within host cells.
- Cord factor (alpha,alpha-trehalose 6,6'-dimycolate) has been implicated in the pathogenesis of tuberculosis.
Purpose of the Study:
- To investigate the direct effect of cord factor on membrane fusion processes.
- To elucidate the mechanism by which cord factor inhibits phagosome-lysosome fusion.
- To explore the implications of these findings for understanding bacterial pathogenesis and developing treatments.
Main Methods:
- Utilized phospholipid vesicles to model cellular membranes.
- Assayed the effect of cord factor on calcium-induced vesicle fusion.
- Proposed a mechanistic explanation for cord factor's inhibitory action.
Main Results:
- Cord factor demonstrated remarkable efficacy in preventing calcium-induced fusion between phospholipid vesicles.
- A mechanism for cord factor's inhibitory effect on membrane fusion was suggested.
Conclusions:
- Cord factor directly interferes with essential membrane fusion events crucial for host cell defense.
- Understanding this mechanism provides insights into the pathogenesis of bacterial diseases.
- These findings may guide the development of novel therapeutic strategies against bacterial infections.