Elucidation of protein biomarkers in plasma and urine for epsilon toxin exposure in mouse model.

Epsilon toxin (ETX) is the major virulence determinant of C. perfringens type B or type D strains, causing diseases in animals, besides being a listed biological and toxin warfare (BTW) agent. Keeping in mind the high lethality and the rapid onset of clinical manifestations, early diagnosis of epsilon toxin exposure is of paramount importance for implementation of appropriate medical countermeasures. Using a 2DE-MS approach, the present study is the first comprehensive proteomic elucidation of ETX-induced protein markers in the mouse model, providing putative targets for early diagnosis of ETX exposure. A total of 52 unique proteins showing ETX-induced modulations were identified in plasma and urine samples. Fibrinogen, apolipoprotein, serum amyloid protein, plasminogen, serum albumin, glutathione peroxidase, transferrin, major urinary protein 2, haptoglobin, transthyretin, and vitamin D-binding protein were among the proteins observed in more than one dataset with altered abundance after the ETX-intoxication. The predicted localization, function, and interaction of the ETX-modulated proteins in the plasma and urine indicated involvement of multiple pathways; extracellular proteins, followed by macromolecular complexes associated with blood coagulation and plasminogen activating cascade, being the most prominent among others. The putative markers elucidated here warrants further validation and can be of immense value for the early diagnosis of ETX exposure.