Anaerobic respiration: In vitro efficacy of Nitazoxanide against mitochondriate Acanthamoeba castellanii of the T4 genotype

Aqeel, Yousuf and Siddiqui, Ruqaiyyah Bano * and Farooq, Maria and Khan, Naveed Ahmed * (2015) Anaerobic respiration: In vitro efficacy of Nitazoxanide against mitochondriate Acanthamoeba castellanii of the T4 genotype. Experimental parasitology, 157. pp. 170-176. ISSN 0014-4894

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Official URL: http://www.sciencedirect.com/science/article/pii/S...

Abstract

Acanthamoeba is an opportunistic protist pathogen that is responsible for serious human and animal infection. Being one of the most frequently isolated protists from the environment, it is likely that it readily encounters microaerophilic environments. For respiration under anaerobic or low oxygen conditions in several amitochondriate protists, decarboxylation of pyruvate is catalyzed by pyruvate ferredoxin oxidoreductase instead of pyruvate dehydrogenase. In support, Nitazoxanide, an inhibitor of pyruvate ferredoxin oxidoreductase, is effective and non-mutagenic clinically against a range of amitochondriate protists, Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. The overall aim of the present study was to determine in vitro efficacy of Nitazoxanide against Acanthamoeba castellanii. At micromolar concentrations, the findings revealed that Nitazoxanide neither affected A. castellanii growth or viability nor amoeba-mediated host cell monolayer damage in vitro or extracellular proteolytic activities. Similarly, microaerophilic conditions alone had no significant effects. In contrast, microaerophilic conditions together with Nitazoxanide showed amoebicidal effects and inhibited A. castellanii-mediated host cell monolayer damage as well as extracellular proteases. Using encystation assays, it was observed that Nitazoxanide inhibited trophozoite transformation into cysts both under aerophilic and microaerophilic conditions. Furthermore, pre-treatment of cysts with Nitazoxanide inhibited A. castellanii excystation. These findings are important in the identification of potential targets that could be useful against parasite-specific respiration as well as to understand the basic biology of the life cycle of Acanthamoeba.

Item Type: Article
Additional Information: First author is with Department of Microbiology, Boston University School of Medicine; 2nd author is with Department of Biological and Biomedical Sciences, Aga Khan University; 3rd author is with Department of Biological Sciences, Faculty of Science and Technology, Sunway University
Uncontrolled Keywords: Acanthamoeba; Pyruvate ferredoxin oxidoreductase; Microaerophilic condition; Nitazoxanide
Subjects: Q Science > QR Microbiology
Divisions: Sunway University > School of Science and Technology > Dept. Biological Sciences
Depositing User: Ms. Molly Chuah
Date Deposited: 28 Mar 2016 07:15
Last Modified: 02 Feb 2017 06:25
URI: http://eprints.sunway.edu.my/id/eprint/314

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