Enzymes involved in pyrophosphate and calcium metabolism as targets for anti-scuticociliate chemotherapy

Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
  • Mallo Seijas, Natalia
  • Lamas Fernández, Jesús
  • Felipe González, Ana Paula de
  • Sueiro Benavides, Rosa Ana
  • Fontenla Iglesias, Francisco
  • Leiro Vidal, José Manuel
This is the peer reviewed version of the following article: Mallo, N., Lamas,
J., DeFelipe, A.P., Sueiro, R.A., Fontenla, F. and Leiro JM. (2016), Enzymes
Involved in Pyrophosphate and Calcium Metabolism as Targets for Antiscuticociliate Chemotherapy. J Eukaryot Microbiol 63(4): 505-15. doi:
10.1111/jeu.12294, which has been published in final form
at https://doi.org/10.1111/jeu.12294. This article may be used for noncommercial purposes in accordance with Wiley Terms and Conditions for
Use of Self-Archived Versions, Inorganic pyrophosphate (PPi) is a key metabolite in cellular bioenergetics under chronic stress conditions in prokaryotes, protists and plants. Inorganic pyrophosphatases (PPases) are essential enzymes controlling the cellular concentration of PPi and mediating intracellular pH and Ca(2+) homeostasis. We report the effects of the antimalarial drugs chloroquine (CQ) and artemisinin (ART) on the in vitro growth of Philasterides dicentrarchi, a scuticociliate parasite of turbot; we also evaluated the action of these drugs on soluble (sPPases) and vacuolar H+-PPases (H+-PPases). CQ and ART inhibited the in vitro growth of ciliates with IC50 values of respectively 74 ± 9 μM and 80 ± 8 μM. CQ inhibits the H+ translocation (with an IC50 of 13.4 ± 0.2 μM), while ART increased translocation of H+ and acidification. However, both drugs caused a decrease in gene expression of H+-PPases. CQ significantly inhibited the enzymatic activity of sPPases, decreasing the consumption of intracellular PPi. ART inhibited intracellular accumulation of Ca(2+) induced by ATP, indicating an effect on the Ca(2+) -ATPase. The results suggest that CQ and ART deregulate enzymes associated with PPi and Ca(2+) metabolism, altering the intracellular pH homeostasis vital for parasite survival and providing a target for the development of new drugs against scuticociliatosis, This study was financially supported by grant AGL2014-57125-R from the Ministerio de Economía y Competitividad (Spain), by the European Commission, under the Horizon 2020 programme (Grant Agreement 634429, PARAFISHCONTROL), and 430 by grant GPC2014/069 from the Xunta de Galicia (Spain), SI
 

DOI: http://hdl.handle.net/10347/18169
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela

HANDLE: http://hdl.handle.net/10347/18169
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
 
Ver en: http://hdl.handle.net/10347/18169
Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela