Trehalose dimycolate (TDM), also known as cord factor, is a potent mycobacterial glycolipid composed of trehalose (α-D-glucopyranosyl-α-D-glucopyranoside) esterified at both 6-positions with mycolic acids, forming a major virulence-associated component of mycobacterial cell envelopes. As one of the most abundant surface-exposed lipids, TDM contributes to cord formation, granuloma induction, and modulation of host macrophage responses, extending the functional diversity of bacterial glycolipids beyond classical lipopolysaccharide structures.

Chemical Structure

Trehalose dimycolate consists of a non-reducing trehalose core symmetrically acylated by two long-chain mycolic acids. The total carbon chain length typically ranges between C60 and C80 per molecule, with α-branch segments of approximately 24–26 carbons and meromycolate chains of 36–54 carbons that may contain cis/trans Δ2–6 unsaturations, hydroxyl groups, or keto substitutions. The estimated molecular formula is approximately C130H250O15 with a molecular weight near 2000 Da, although natural structural heterogeneity is common due to variations in mycolic acid subclasses including α-mycolates, methoxymycolates, and ketomycolates, which influence biological activity and toxicity. Microscopic imaging of mycobacterial cells shows rod-shaped bacterial clusters forming serpentine cord-like arrangements, a phenotype stabilized by surface monolayers enriched in trehalose dimycolate.

Physical Properties

Trehalose dimycolate is an amphiphilic glycolipid characterized by an exceptionally large hydrophobic domain that promotes spontaneous monolayer assembly at hydrophobic–hydrophilic interfaces. In aqueous environments, TDM can organize into micellar or multilamellar structures that exhibit strong resistance to dehydration. The lipid exhibits relatively high thermal transition stability, with melting behavior typically above 60°C, reflecting highly ordered crystalline packing within lipid assemblies. TDM is soluble in organic solvent systems such as chloroform–methanol mixtures and has reported optical rotation values around [α]D +32° to +35° under standardized conditions.