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Home / Equine Research Bank / Antimicrob Agents Chemother / Killing of Trypanozoon Parasites by the Equine Cathelicidin ...
Antimicrobial agents and chemotherapy2016; 60(5); 2610-2619; doi: 10.1128/AAC.01127-15

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1.

Abstract: 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 (IC50) 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.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
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Publication Date: 2016-04-22 PubMed ID: 26824936PubMed Central: PMC4862532DOI: 10.1128/AAC.01127-15Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the effectiveness of the equine antimicrobial peptide eCATH1 in killing Trypanozoon parasites, who cause diseases such as sleeping sickness in humans and nagana and surra in animals. The study finds that eCATH1 displays significant inhibitory activity against different species of the parasite and damages their cellular structures, suggesting potential for development into novel therapeutic agents.

Research Objective and Background

  • This study aimed to explore potential antiparasitic agents to combat Trypanozoon parasites, responsible for diseases like sleeping sickness, nagana, surra, and dourine.
  • The need for new treatments arises due to the rising drug resistance against existing chemotherapy treatments used in managing nagana and surra, and the absence of an official therapy for dourine.
  • The research builds upon previous studies of the equine antimicrobial peptide eCATH1, which has shown effectiveness against equine Gram-positive and Gram-negative bacteria without harmful effects on mammalian cells.

Study Design and Findings

  • The research evaluates eCATH1’s inhibitory activity against Trypanosoma brucei brucei, Trypanosoma evansi, and Trypanosoma equiperdum, reporting an in vitro 50% inhibitory concentration (IC50) of 9.5 μM.
  • It was found that eCATH1 kills the parasites by disrupting their plasma membranes and damaging their mitochondria.
  • This observation was supported by evidence showing eCATH1’s rapid induction of SYTOX Green influx, disruption of mitochondrial membrane potential as revealed through immunofluorescence microscopy, and noticeable damage to the membrane and intracellular structures of the parasites within 15 min of exposure at 9.5 μM.
  • The study also found that administering eCATH1 to mice infected by Trypanosoma equiperdum at a 10 mg/kg dose delayed mortality.

Implications and Conclusions

  • The research suggests that eCATH1 demonstrates significant potential in the development of novel therapeutic agents against trypanosome infections.
  • However, further research is needed to validate these findings and to explore the potential side effects and the most effective dose of eCATH1.

Cite This Article

APA
Cauchard S, Van Reet N, Büscher P, Goux D, Grötzinger J, Leippe M, Cattoir V, Laugier C, Cauchard J. (2016). Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1. Antimicrob Agents Chemother, 60(5), 2610-2619. https://doi.org/10.1128/AAC.01127-15

Publication

Antimicrobial agents and chemotherapy
ISSN: 1098-6596
NlmUniqueID: 0315061
Country: United States
Language: English
Volume: 60
Issue: 5
Pages: 2610-2619

Researcher Affiliations

Cauchard, S
  • ANSES, Dozule Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, France Université de Caen Basse-Normandie, EA4655 U2RM (Équipe Antibio-Résistance), Caen, France.
Van Reet, N
  • Unit of Parasite Diagnostics, Department of Biomedical Sciences, Institute for Tropical Medicine, Antwerp, Belgium.
Büscher, P
  • Unit of Parasite Diagnostics, Department of Biomedical Sciences, Institute for Tropical Medicine, Antwerp, Belgium.
Goux, D
  • Centre de Microscopie Appliquée à la Biologie, SF4206 ICORE, Université de Caen Basse-Normandie, France.
Grötzinger, J
  • Institute of Biochemistry, Christian-Albrechts University of Kiel, Kiel, Germany.
Leippe, M
  • Zoological Institute, Comparative Immunobiology, Christian-Albrechts University of Kiel, Kiel, Germany.
Cattoir, V
  • Université de Caen Basse-Normandie, EA4655 U2RM (Équipe Antibio-Résistance), Caen, France CHU de Caen, Service de Microbiologie, Caen, France CNR de la Résistance aux Antibiotiques, Laboratoire Associé Entérocoques, Caen, France.
Laugier, C
  • ANSES, Dozule Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, France.
Cauchard, J
  • ANSES, Dozule Laboratory for Equine Diseases, Bacteriology and Parasitology Unit, Goustranville, France julien.cauchard@anses.fr.

MeSH Terms

  • Animals
  • Antimicrobial Cationic Peptides / pharmacology
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Inhibitory Concentration 50
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Trypanocidal Agents / pharmacology
  • Trypanosoma / drug effects
  • Trypanosoma brucei brucei / drug effects

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Citations

This article has been cited 5 times.
  1. Rojas-Pirela M, Kemmerling U, Quiñones W, Michels PAM, Rojas V. Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?. Biomolecules 2023 Mar 26;13(4).
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  2. El-Dirany R, Shahrour H, Dirany Z, Abdel-Sater F, Gonzalez-Gaitano G, Brandenburg K, Martinez de Tejada G, Nguewa PA. Activity of Anti-Microbial Peptides (AMPs) against Leishmania and Other Parasites: An Overview.. Biomolecules 2021 Jul 4;11(7).
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  3. Kumar R, Ali SA, Singh SK, Bhushan V, Mathur M, Jamwal S, Mohanty AK, Kaushik JK, Kumar S. Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects.. Vet Sci 2020 Dec 18;7(4).
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  4. Scheenstra MR, van Harten RM, Veldhuizen EJA, Haagsman HP, Coorens M. Cathelicidins Modulate TLR-Activation and Inflammation.. Front Immunol 2020;11:1137.
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  5. Scheenstra MR, van den Belt M, Tjeerdsma-van Bokhoven JLM, Schneider VAF, Ordonez SR, van Dijk A, Veldhuizen EJA, Haagsman HP. Cathelicidins PMAP-36, LL-37 and CATH-2 are similar peptides with different modes of action.. Sci Rep 2019 Mar 18;9(1):4780.
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