Amoebicidal Activity of Caffeine and Maslinic Acid by the Induction of Programmed Cell Death in Acanthamoeba.
Free-living amoebae of the genusAcanthamoebaare the causal agents of a sight-threatening ulceration of the cornea calledAcanthamoebakeratitis, as well as the rare but usually fatal disease granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment ofAcanthamoebainfections, they are generally lengthy and/or have limited efficacy. For the best clinical outcome, treatments should target both the trophozoite and the cyst stages, as cysts are known to confer resistance to treatment. In this study, we document the activities of caffeine and maslinic acid against both the trophozoite and the cyst stages of three clinical strains ofAcanthamoebaThese drugs were chosen because they are reported to inhibit glycogen phosphorylase, which is required for encystation. Maslinic acid is also reported to be an inhibitor of extracellular proteases, which may be relevant since the protease activities ofAcanthamoebaspecies are correlated with their pathogenicity. We also provide evidence for the first time that both drugs exert their anti-amoebal effects through programmed cell death.
University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
Carmen M
CM
Martín-Navarro
University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain.|Microbiologie de l'eau, Laboratoire Ecologie et Biologie des Interactions, UMR CNRS 7267, Université de Poitiers, Poitiers, France.
Atteneri
A
López-Arencibia
University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain.|Laboratoire Matériaux-Molécules et Applications, IPEST, La Marsa, University of Carthage, Tunisia.
Ines
I
Sifaoui
University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
María
M
Reyes-Batlle
Microbiologie de l'eau, Laboratoire Ecologie et Biologie des Interactions, UMR CNRS 7267, Université de Poitiers, Poitiers, France.
Emilie
E
Fouque
Molecular Biochemistry and Parasitology Research Group, Department of Parasitology, Faculty of Sciences, Institute of Biotechnology, University of Granada, Granada, Spain.
Antonio
A
Osuna
University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
Basilio
B
Valladares
University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain.
José E
JE
Piñero
Microbiologie de l'eau, Laboratoire Ecologie et Biologie des Interactions, UMR CNRS 7267, Université de Poitiers, Poitiers, France.
Yann
Y
Héchard
Centre for Integrative Physiology, Biomedical Sciences, Edinburgh Medical School, University of Edinburgh, Scotland, United Kingdom.
Sutherland K
SK
Maciver
University Institute of Tropical Diseases and Public Health of the Canary Islands, Universidad de La Laguna, Tenerife, Canary Islands, Spain jmlorenz@ull.edu.es.
Jacob
J
Lorenzo-Morales
D000048:Acanthamoeba / Q000187:drug effects* / Q000378:metabolism*; D000563:Amebicides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D053058:Trophozoites / Q000187:drug effects; D009828:Oleanolic Acid / Q000031:analogs & derivatives
D000563:Amebicides; D002110:Caffeine; D014315:Triterpenes; C412811:maslinic acid; D009828:Oleanolic Acid
Acanthamoeba; PCD; caffeine, maslinic acid, programmed cell death