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Updated: Mar 24, 2026

Rapid One-step Enzymatic Synthesis and All-aqueous Purification of Trehalose Analogues
Published on: February 17, 2017
Trehalose 6,6-Dimycolate from Mycobacterium tuberculosis Induces Hypercoagulation.
Elizabeth Donnachie1, Elena P Fedotova2, Shen-An Hwang3
1Gulf States Hemophilia and Thrombophilia Center, Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas.
Trehalose 6,6-dimycolate (TDM) can induce inflammation and hypercoagulopathy in a new mouse model. This study shows TDM alone is sufficient to cause the blood clotting issues seen in tuberculosis patients.
Area of Science:
- Immunology
- Pathology
- Hematology
Background:
- Tuberculosis (TB) is a global health issue.
- Trehalose 6,6-dimycolate (TDM) is implicated in TB pathogenesis, activating innate and chronic inflammation.
- Existing noninfectious TB models using TDM emulsions replicate some patient pathologies.
Purpose of the Study:
- To develop a novel, noninfectious mouse model using TDM to study TB-related inflammation and vascular pathology.
- To investigate the role of TDM in promoting inflammatory lung findings, vascular occlusion, hemorrhage, and hypercoagulopathy.
Main Methods:
- Mice (C57BL/6 and BALB/c) received intraperitoneal (i.p.) TDM followed by intravenous (i.v.) TDM (TDM-IPIV) or single i.p. or i.v. TDM injections.
- Evaluated inflammatory responses, cytokine profiles (including IL-10 and GM-CSF), T-cell populations (CD4+), and coagulation parameters.
- Assessed vascular changes using Masson's trichrome staining for collagen deposition.
Main Results:
- The TDM-IPIV model induced significant inflammatory lung pathology and increased inflammatory and T-cell cytokines in both mouse strains.
- The TDM-IPIV group exhibited enhanced IL-10 and granulocyte-macrophage colony-stimulating factor levels and increased CD4+ T cells in lung tissue.
- Hypercoagulopathy was observed in the TDM-IPIV group, characterized by increased coagulation, reduced clot formation time, and increased clot firmness, with collagen deposition in occluded vasculature.
- These TDM-induced effects on coagulation were independent of the observed inflammation.
Conclusions:
- The novel TDM-IPIV mouse model effectively replicates key inflammatory and vascular pathologies seen in TB.
- TDM is sufficient to induce a state of hypercoagulopathy, suggesting a direct role in the coagulation abnormalities observed in TB patients.
- This model provides a valuable tool for studying TB pathogenesis and developing targeted therapies for associated complications.

