Statins and voriconazole induce programmed cell death in Acanthamoeba castellanii

Antimicrobial Agents and Chemotherapy
Carmen M Martín-NavarroJacob Lorenzo-Morales

Abstract

Members of the genus Acanthamoeba are facultative pathogens of humans, causing a sight-threatening keratitis and a life-threatening encephalitis. In order to treat those infections properly, it is necessary to target the treatment not only to the trophozoite but also to the cyst. Furthermore, it may be advantageous to avoid parasite killing by necrosis, which may induce local inflammation. We must also avoid toxicity of host tissue. Many drugs which target eukaryotes are known to induce programmed cell death (PCD), but this process is poorly characterized in Acanthamoeba. Here, we study the processes of programmed cell death in Acanthamoeba, induced by several drugs, such as statins and voriconazole. We tested atorvastatin, fluvastatin, simvastatin, and voriconazole at the 50% inhibitory concentrations (IC50s) and IC90s that we have previously established. In order to evaluate this phenomenon, we investigated the DNA fragmentation, one of the main characteristics of PCD, with quantitative and qualitative techniques. Also, the changes related to phosphatidylserine exposure on the external cell membrane and cell permeability were studied. Finally, because caspases are key to PCD pathways, caspase activity was evaluated in Acantha...Continue Reading

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Citations

Nov 12, 2016·Survey of Ophthalmology·Linda Christian Carrijo-CarvalhoFabio Ramos de Souza Carvalho
May 4, 2017·Journal of Basic Microbiology·Abdul M BaigNaveed A Khan
Mar 23, 2017·Antimicrobial Agents and Chemotherapy·Carmen M Martín-NavarroJacob Lorenzo-Morales
May 3, 2019·FEMS Microbiology Reviews·Ascel Samba-LouakaYann Héchard
Aug 8, 2018·Infectious Disorders Drug Targets·Ritika RanaAnoop Kumar
Jun 6, 2018·Scientific Reports·Ines SifaouiJacob Lorenzo-Morales
Aug 11, 2019·Pathogens·Aitor Rizo-LiendoJacob Lorenzo-Morales
Oct 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ignasi B VerdaguerAlejandro M Katzin
Feb 26, 2020·Antimicrobial Agents and Chemotherapy·Brian ShingAnjan Debnath
May 28, 2020·Pathogens·Hany M ElsheikhaNaveed Ahmed Khan
Nov 25, 2020·Antimicrobial Agents and Chemotherapy·Víctor Sebastián-PérezCarmen Gil
Feb 9, 2021·Bioorganic Chemistry·Rubén L Rodríguez-ExpósitoJacob Lorenzo-Morales
Jul 26, 2018·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Wenxu ZhouW David Nes
Jan 17, 2019·Experimental Parasitology·Dolores Hernández-MartínezMaritza Omaña-Molina
Aug 4, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Aitor Rizo-LiendoJacob Lorenzo-Morales
Aug 20, 2021·International Journal for Parasitology. Drugs and Drug Resistance·Rubén L Rodríguez-ExpósitoJacob Lorenzo-Morales
Mar 11, 2020·Journal français d'ophtalmologie·K BrunetE Cateau
Oct 5, 2021·Pathogens and Global Health·Mohammad Ridwane MungrooRuqaiyyah Siddiqui

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