Mefloquine interferes with glycolysis in schistosomula of Schistosoma mansoni via inhibition of enolase

Manneck, Theresia; Keiser, Jennifer; Müller, Joachim (2012). Mefloquine interferes with glycolysis in schistosomula of Schistosoma mansoni via inhibition of enolase. Parasitology, 139(4), pp. 497-505. Cambridge University Press 10.1017/S0031182011002204

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The antimalarial drug mefloquine has promising antischistosomal properties killing haematophagous adult schistosomes as well as schistosomula. The mode of action and involved drug targets of mefloquine in Schistosoma mansoni schistosomula are unknown. In order to identify mefloquine-binding proteins and thus potential drug targets, mefloquine affinity chromatography with S. mansoni schistosomula crude extracts was performed. We found one specific mefloquine-binding protein that was identified by mass spectrometry as the glycolytic enzyme enolase (Q27877). Enolase activity assays were performed on schistosomula crude extracts and on the recombinant enolase Q27877 expressed in Escherichia coli. In schistosomula crude extracts enolase activity was inhibited by mefloquine and by the enolase inhibitor sodium fluoride, while activity of the recombinant enolase was not affected. In contrast to enolase from crude extracts, recombinant Q27877 did not bind to mefloquine-agarose. Using isothermal microcalorimetry, we next investigated the metabolic inhibition of mefloquine and 3 known glycolytic inhibitors in Schistosoma spp., namely sodium fluoride, 3-bromopyruvate and menadione on schistosomula in the presence or absence of glucose. We found that in the presence of glucose, schistosomula were less affected by mefloquine, sodium fluoride and 3-bromopyruvate, whereas glucose had no protective effect when schistosomula had been exposed to menadione. These results suggest a potential role of mefloquine as an inhibitor of glycolysis, at least in stages where other targets like haem degradation are not relevant.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology

UniBE Contributor:

Müller, Joachim

Subjects:

600 Technology > 630 Agriculture

ISSN:

0031-1820

Publisher:

Cambridge University Press

Language:

English

Submitter:

Marceline Brodmann

Date Deposited:

14 Jul 2020 15:07

Last Modified:

26 Jul 2020 13:11

Publisher DOI:

10.1017/S0031182011002204

PubMed ID:

22309769

BORIS DOI:

10.7892/boris.115683

URI:

https://boris.unibe.ch/id/eprint/115683

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