5 Cording, Cord Factors, and Trehalose Dimycolate

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This chapter has two purposes. The first is to review the chemistry, biosynthesis, biologic activity, and pathogenic function for trehalose dimycolate (TDM). The second purpose of the chapter is to review the history, genetic determinants, and biochemical basis of the cording morphology. The historical controversy about the relationship between cording and TDM has been partially clarified by recent studies, which are used as the basis for the attempts to summarize the importance of TDM and cording in mycobacterial pathogenesis. Cording must be distinguished from clumping, which is a general property of mycobacteria owing to their hydrophobic surface. Characterization of null mutants of BCG and revealed a strain that lacked the proximal cyclopropane ring of the alpha mycolic acid. Genetic analyses of the cording morphology in have identified multiple genes that are necessary for the expression of the cording morphology. Chemical characterization of the active compound revealed, a glycolipid whose common name became “cord factor” based on its derivation from Bloch’s petroleum ether extracts. A biochemical screen for the molecular basis for mycolic acid transfer from glucose monomycolate (GMM) to free trehalose identified antigen 85 A-C. Each of the proteins transferred a mycolic acid from glucose monomycolate to free trehalose or GMM to produce GMM or TDM respectively. TDM can be isolated from all mycobacteria that synthesize mycolic acids. Cording remains a reliable predictor of attenuation and in many cases is due to loss of specific cell envelope lipids.

Citation: S. Glickman M. 2008. 5 Cording, Cord Factors, and Trehalose Dimycolate, p 63-73. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch5
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Image of Figure 1.
Figure 1.

Erdman grown without detergent and stained with auramine rhodamine. Characteristic cording in which the bacteria align along their long axes to form linear strands is visible.

Citation: S. Glickman M. 2008. 5 Cording, Cord Factors, and Trehalose Dimycolate, p 63-73. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch5
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Image of Figure 2.
Figure 2.

The chemical structure at the top is trehalose dimycolate. Esterified to the trehalose headgroup are two mycolic acids. In this example, cyclopropanated ketomycolate and alpha mycolate are pictured. The two mycolic acid positions can be occupied by any combination of mycolic acids, making TDM isolated from bacteria a complex mixture of compounds. The space-filling model is of the same TDM pictured on the top with the relevant functional groups indicated.

Citation: S. Glickman M. 2008. 5 Cording, Cord Factors, and Trehalose Dimycolate, p 63-73. In Daffé M, Reyrat J, Avenir G (ed), The Mycobacterial Cell Envelope. ASM Press, Washington, DC. doi: 10.1128/9781555815783.ch5
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