Amoebicidal Activity of Caffeine and Maslinic Acid by the Induction of Programmed Cell Death in Acanthamoeba

• Published in: Antimicrobial agents and chemotherapy Vol. 61; no. 6
• Main Authors: Martín-Navarro, Carmen M, López-Arencibia, Atteneri, Sifaoui, Ines, Reyes-Batlle, María, Fouque, Emilie, Osuna, Antonio, Valladares, Basilio, Piñero, José E, Héchard, Yann, Maciver, Sutherland K, Lorenzo-Morales, Jacob
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.06.2017
• Subjects: Acanthamoeba; Acanthamoeba - drug effects; Acanthamoeba - metabolism; Amebicides; Amebicides - pharmacology; Apoptosis - drug effects; Biochemistry, Molecular Biology; Caffeine; Caffeine - pharmacology; Experimental Therapeutics; Life Sciences; Microbiology and Parasitology; Triterpenes; Triterpenes - pharmacology; Trophozoites - drug effects; PCD; Acanthamoeba; caffeine, maslinic acid, programmed cell death; caffeine; maslinic acid; programmed cell death
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.02660-16

Free-living amoebae of the genus are the causal agents of a sight-threatening ulceration of the cornea called keratitis, as well as the rare but usually fatal disease granulomatous amoebic encephalitis. Although there are many therapeutic options for the treatment of infections, 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 of These 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 of species 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.