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Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin.
Int J Antimicrob Agents. 2015 Nov; 46(5):546-51.IJ

Abstract

This study investigated the effects of oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine (MEF) and identified proteins that bind to MEF in parasite extracts and human cells by affinity chromatography. In a pilot experiment, MEF treatment was applied 5 days per week and was intensified by increasing the dosage stepwise from 12.5 mg/kg to 200 mg/kg during 4 weeks followed by treatments of 100 mg/kg during the last 7 weeks. This resulted in a highly significant reduction of parasite weight in MEF-treated mice compared with mock-treated mice, but the reduction was significantly less efficacious compared with the standard treatment regimen of albendazole (ABZ). In a second experiment, MEF was applied orally in three different treatment groups at dosages of 25, 50 or 100 mg/kg, but only twice a week, for a period of 12 weeks. Treatment at 100 mg/kg had a profound impact on the parasite, similar to ABZ treatment at 200 mg/kg/day (5 days/week for 12 weeks). No adverse side effects were noted. To identify proteins in E. multilocularis metacestodes that physically interact with MEF, affinity chromatography of metacestode extracts was performed on MEF coupled to epoxy-activated Sepharose(®), followed by SDS-PAGE and in-gel digestion LC-MS/MS. This resulted in the identification of E. multilocularis ferritin and cystatin as MEF-binding proteins. In contrast, when human cells were exposed to MEF affinity chromatography, nicotinamide phosphoribosyltransferase was identified as a MEF-binding protein. This indicates that MEF could potentially interact with different proteins in parasites and human cells.

Authors+Show Affiliations

Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland.Institute of Parasitology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, CH-3012 Bern, Switzerland. Electronic address: andrew.hemphill@vetsuisse.unibe.ch.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26395219

Citation

Küster, Tatiana, et al. "Oral Treatments of Echinococcus Multilocularis-infected Mice With the Antimalarial Drug Mefloquine That Potentially Interacts With Parasite Ferritin and Cystatin." International Journal of Antimicrobial Agents, vol. 46, no. 5, 2015, pp. 546-51.
Küster T, Stadelmann B, Rufener R, et al. Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin. Int J Antimicrob Agents. 2015;46(5):546-51.
Küster, T., Stadelmann, B., Rufener, R., Risch, C., Müller, J., & Hemphill, A. (2015). Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin. International Journal of Antimicrobial Agents, 46(5), 546-51. https://doi.org/10.1016/j.ijantimicag.2015.07.016
Küster T, et al. Oral Treatments of Echinococcus Multilocularis-infected Mice With the Antimalarial Drug Mefloquine That Potentially Interacts With Parasite Ferritin and Cystatin. Int J Antimicrob Agents. 2015;46(5):546-51. PubMed PMID: 26395219.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine that potentially interacts with parasite ferritin and cystatin. AU - Küster,Tatiana, AU - Stadelmann,Britta, AU - Rufener,Reto, AU - Risch,Corina, AU - Müller,Joachim, AU - Hemphill,Andrew, Y1 - 2015/09/02/ PY - 2015/06/15/received PY - 2015/07/22/revised PY - 2015/07/23/accepted PY - 2015/9/24/entrez PY - 2015/9/24/pubmed PY - 2016/8/25/medline KW - Alveolar echinococcosis KW - Chemotherapy KW - Cystatin KW - Ferritin KW - Mefloquine KW - Nicotinamide phosphoribosyltransferase SP - 546 EP - 51 JF - International journal of antimicrobial agents JO - Int. J. Antimicrob. Agents VL - 46 IS - 5 N2 - This study investigated the effects of oral treatments of Echinococcus multilocularis-infected mice with the antimalarial drug mefloquine (MEF) and identified proteins that bind to MEF in parasite extracts and human cells by affinity chromatography. In a pilot experiment, MEF treatment was applied 5 days per week and was intensified by increasing the dosage stepwise from 12.5 mg/kg to 200 mg/kg during 4 weeks followed by treatments of 100 mg/kg during the last 7 weeks. This resulted in a highly significant reduction of parasite weight in MEF-treated mice compared with mock-treated mice, but the reduction was significantly less efficacious compared with the standard treatment regimen of albendazole (ABZ). In a second experiment, MEF was applied orally in three different treatment groups at dosages of 25, 50 or 100 mg/kg, but only twice a week, for a period of 12 weeks. Treatment at 100 mg/kg had a profound impact on the parasite, similar to ABZ treatment at 200 mg/kg/day (5 days/week for 12 weeks). No adverse side effects were noted. To identify proteins in E. multilocularis metacestodes that physically interact with MEF, affinity chromatography of metacestode extracts was performed on MEF coupled to epoxy-activated Sepharose(®), followed by SDS-PAGE and in-gel digestion LC-MS/MS. This resulted in the identification of E. multilocularis ferritin and cystatin as MEF-binding proteins. In contrast, when human cells were exposed to MEF affinity chromatography, nicotinamide phosphoribosyltransferase was identified as a MEF-binding protein. This indicates that MEF could potentially interact with different proteins in parasites and human cells. SN - 1872-7913 UR - https://www.unboundmedicine.com/medline/citation/26395219/Oral_treatments_of_Echinococcus_multilocularis_infected_mice_with_the_antimalarial_drug_mefloquine_that_potentially_interacts_with_parasite_ferritin_and_cystatin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0924-8579(15)00286-1 DB - PRIME DP - Unbound Medicine ER -