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Induction of Programmed Cell Death in Acanthamoeba culbertsoni by the Repurposed Compound Nitroxoline
Rubén L Rodríguez-Expósito1,2, Ines Sifaoui1,2, María Reyes-Batlle1,2
1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), Universidad de La Laguna (ULL), Avda. Astrofísico Fco. Sánchez, S/N, 38203 San Cristóbal de La Laguna, Spain.
Abstract:
Acanthamoeba is a ubiquitous genus of amoebae that can act as opportunistic parasites in both humans and animals, causing a variety of ocular, nervous and dermal pathologies. Despite advances in Acanthamoeba therapy, the management of patients with Acanthamoeba infections remains a challenge for health services. Therefore, there is a need to search for new active substances against Acanthamoebae. In the present study, we evaluated the amoebicidal activity of nitroxoline against the trophozoite and cyst stages of six different strains of Acanthamoeba. The strain A. griffini showed the lowest IC50 value in the trophozoite stage (0.69 ± 0.01 µM), while the strain A. castellanii L-10 showed the lowest IC50 value in the cyst stage (0.11 ± 0.03 µM). In addition, nitroxoline induced in treated trophozoites of A. culbertsoni features compatibles with apoptosis and autophagy pathways, including chromatin condensation, mitochondrial malfunction, oxidative stress, changes in cell permeability and the formation of autophagic vacuoles. Furthermore, proteomic analysis of the effect of nitroxoline on trophozoites revealed that this antibiotic induced the overexpression and the downregulation of proteins involved in the apoptotic process and in metabolic and biosynthesis pathways.
Insights
Nitroxoline demonstrates potent amoebicidal activity against Acanthamoeba, effectively targeting both trophozoite and cyst stages. This study highlights nitroxoline
Area of Science:
- Microbiology
- Parasitology
- Pharmacology
Background:
- Acanthamoeba are opportunistic parasites causing significant human and animal pathologies.
- Current Acanthamoeba treatments present challenges, necessitating novel therapeutic agents.
Purpose of the Study:
- To evaluate the amoebicidal efficacy of nitroxoline against Acanthamoeba.
- To investigate the molecular mechanisms underlying nitroxoline's action.
Main Methods:
- Testing nitroxoline's activity against trophozoite and cyst stages of six Acanthamoeba strains.
- Inducing apoptosis and autophagy in Acanthamoeba trophozoites with nitroxoline.
- Performing proteomic analysis to identify affected cellular pathways.
Main Results:
- Nitroxoline exhibited significant amoebicidal activity, with low IC50 values against specific Acanthamoeba strains in both trophozoite and cyst forms.
- Nitroxoline induced apoptosis- and autophagy-related cellular changes in Acanthamoeba trophozoites.
- Proteomic analysis revealed nitroxoline's impact on proteins involved in apoptosis and metabolic pathways.
Conclusions:
- Nitroxoline is a promising candidate for treating Acanthamoeba infections.
- Nitroxoline's mechanism involves inducing programmed cell death and disrupting essential cellular processes in Acanthamoeba.
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