Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1
| Autor: | Vincent Cattoir, Claire Laugier, Julien Cauchard, Matthias Leippe, Joachim Grötzinger, Philippe Büscher, S. Cauchard, N Van Reet, Didier Goux |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Trypanosoma Trypanosoma brucei brucei Trypanosoma brucei Rhodamine 123 Microbiology Inhibitory Concentration 50 Mice 03 medical and health sciences chemistry.chemical_compound Microscopy Electron Transmission Animals Experimental Therapeutics Pharmacology (medical) Trypanocidal agent Membrane Potential Mitochondrial Pharmacology biology Chemistry Cell Membrane Trypanosoma evansi biology.organism_classification Surra Trypanocidal Agents Antiparasitic agent 030104 developmental biology Infectious Diseases Microscopy Fluorescence Microscopy Electron Scanning Trypanosoma equiperdum Antimicrobial Cationic Peptides |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 60:2610-2619 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Trypanozoon parasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. Control of nagana and surra depends to a great extent on chemotherapy. However, drug resistance to several of the front-line drugs is rising. Furthermore, there is no official treatment for dourine. Therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. Host defense peptides have recently gained attention as promising candidates. We have previously reported that one such peptide, the equine antimicrobial peptide eCATH1, is highly active against equine Gram-positive and Gram-negative bacteria, without cytotoxicity against mammalian cells at bacteriolytic concentrations. In the present study, we show that eCATH1 exhibits an in vitro 50% inhibitory concentration (IC 50 ) of 9.5 μM against Trypanosoma brucei brucei , Trypanosoma evansi , and Trypanosoma equiperdum . Its trypanocidal mechanism involves plasma membrane permeabilization and mitochondrial alteration based on the following data: (i) eCATH1 induces the rapid influx of the vital dye SYTOX Green; (ii) it rapidly disrupts mitochondrial membrane potential, as revealed by immunofluorescence microscopy using the fluorescent dye rhodamine 123; (iii) it severely damages the membrane and intracellular structures of the parasites as early as 15 min after exposure at 9.5 μM and 5 min after exposure at higher concentrations (19 μM), as evidenced by scanning and transmission electron microscopy. We also demonstrate that administration of eCATH1 at a dose of 10 mg/kg to T. equiperdum -infected mice delays mortality. Taken together, our findings suggest that eCATH1 is an interesting template for the development of novel therapeutic agents in the treatment of trypanosome infections. |
| Databáze: | OpenAIRE |
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