title: Host response to intravenous injection of epsilon toxin in mouse model: a proteomic view.
abstract: Epsilon toxin (ETX) is an extremely potent pore-forming toxin and a category B biological agent. ETX is a major virulence determinant of Clostridium perfringens toxinotypes B and D, and is implicated in pathogenesis of rapidly fatal economically important pulpy kidney disease in lambs caused by toxinotype D. Despite being a toxin, ETX can be utilized as a tool to target glutamatergic neurons and for drug delivery into the CNS. 2DE-MS approach was employed to elucidate the host response to ETX following intravenous injection in mouse model. In total, 136 proteins were identified either differentially expressed in brain (18) and kidney (33); showing specific interaction with ETX from lysates of brain (4), kidney (21), or from plasma (42); and urine markers (18) of intoxication. Differentially expressed proteins in kidney included those involved in calcium homeostasis and cytoskeletal organization. Proteins involved in ER and oxidative stress and energy metabolism also showed differential levels in the target tissue after ETX treatment. The known functions of the proteins differentially expressed and those interacting with ETX indicate involvement of interlinked pathways. This study provides first proteomic account of host response to ETX exposure providing clues to mechanism of toxicity and potential therapeutic targets.
authors.affiliation: Biotechnology Division, Defence Research & Development Establishment, Gwalior, India.
authors.forename: Bhoj
authors.initials: B
authors.lastname: Kumar
authors.forename: Syed Imteyaz
authors.initials: SI
authors.lastname: Alam
authors.forename: Om
authors.initials: O
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000633:toxicity; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001921:Brain / Q000378:metabolism; D003015:Clostridium Infections / Q000378:metabolism / Q000662:veterinary; D003016:Clostridium perfringens / Q000378:metabolism / Q000472:pathogenicity; D004195:Disease Models, Animal; D054884:Host-Pathogen Interactions; D006801:Humans; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000378:metabolism / Q000662:veterinary; D051379:Mice; D011506:Proteins / Q000302:isolation & purification / Q000378:metabolism; D012756:Sheep / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D015415:Biomarkers; D011506:Proteins