<i>In vitro</i>effectiveness of the antimicrobial peptide eCATH1 against antibiotic-resistant bacterial pathogens of horses

Schlusselhuber, Margot; Guldbech, Kristen; Leippe, Matthias; Pétry, Sandrine; Grötzinger, Joachim; Giguère, Steeve; Cauchard, Julien

doi:10.1111/1574-6968.12337

Cited by 7 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, comparisons to other IC 50 s of AMPs should be carefully analyzed, given the different protocols described in the literature for their evaluation (26,(31)(32)(33). The concentrations of eCATH1 used in this study that revealed trypanocidal activity in vitro were 2-fold to 15-fold higher than those sufficient to kill various Grampositive and Gram-negative bacteria (34). Such a difference between the activities against bacteria and parasites had also been observed previously for cathelicidins (26).…”

Section: Discussionsupporting

confidence: 70%

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1

Cauchard

Reet

Büscher

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

h 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 M 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 M and 5 min after exposure at higher concentrations (19 M), 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.

show abstract

Section: Discussionsupporting

confidence: 70%

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1

Cauchard

Reet

Büscher

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…They also tested eCATH1 against equine isolates of E.coli ,S.enterica , K. pneumoniae , Pseudomonas spp . andRhodococcus equi with MICs ranging from 0.5-16 μg/ mL (Schlusselhuber et al, 2014). It was also reported that eCATH1 anin vitro IC50 of 9.5μM against Trypanosoma brucei, Trypanosoma evansi and Trypanosoma equiperdum (Cauchard et al, 2016).…”

Section: Equine Cathelicidinmentioning

confidence: 94%

Antimicrobial Peptides in Farm animals: An updated review on its diversity, function, mode of action and therapeutic prospects

Kumar¹,

Ali²,

Singh³

et al. 2020

Preprint

View full text Add to dashboard Cite

Antimicrobial peptides (AMPs) are the arsenals of the innate host defense system exhibiting the ancient evolutionarily conserved characteristics that is present in practically all forms of life. Recent years have witnessed emergence of antibiotic resistant bacteria compounded with a slow discovery rate for new antibiotics that has necessitated scientific efforts to search for alternatives to antibiotics. Research on the identification of AMPs has generated very encouraging evidences that they curb infectious pathologies and are also useful as novel biologics to function as immunotherapeutic agents. Being innate, they exhibit least toxicity to the host and exert wide spectrum of biological activity including low resistance among microbes, and increased wound healing actions. Notably, in veterinary science, the constant practice of massive doses of antibiotics with inappropriate withdrawal programs led to the high risk of livestock-associated antimicrobial resistance. Therefore, the world faces tremendous pressure for designing and devising strategies to mitigate the use of antibiotics in animals and keep it safe for the posterity. In this review, we illustrate the diversity of farm animals specific AMPs, their biochemical foundations, mode of action and prospective application in clinics. Subsequently, we present the data for their systematic classification by the major and minor groups, antipathogenic action, and allied bioactivities in the host. Finally, we address the limitations to their clinical implementation and envision areas for further advancement.

show abstract

Application of Synthetic Molecular Evolution to the Discovery of Antimicrobial Peptides

Wimley

2019

Advances in Experimental Medicine and Biology

View full text Add to dashboard Cite

In vitroeffectiveness of the antimicrobial peptide eCATH1 against antibiotic-resistant bacterial pathogens of horses

Cited by 7 publications

References 13 publications

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1

Killing of Trypanozoon Parasites by the Equine Cathelicidin eCATH1

Antimicrobial Peptides in Farm animals: An updated review on its diversity, function, mode of action and therapeutic prospects

Application of Synthetic Molecular Evolution to the Discovery of Antimicrobial Peptides

Contact Info

Product

Resources

About