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Potential Inhibitors of Human-Naegleria fowleri Interactions: An In Vitro Extracellular Matrix-Based Model
Javier Chao-Pellicer1,2,3, Iñigo Arberas-Jiménez1,2, Ines Sifaoui1,2,3
1Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain.
Abstract:
Primary amoebic meningoencephalitis (PAM) is a rapidly progressive and fulminant disease that affects the central nervous system caused by the free-living amoeba Naegleria fowleri. The adhesion to extracellular matrix (ECM) proteins is considered as one of the key steps in the success of the infection and could represent an interesting target to be explored in the prevention and treatment of the disease. In this work, the effect of two sesquiterpenes with proven anti-Naegleria activity on the adhesion of the parasite was evaluated using an in vitro ECM-based model, compared with the reference drugs amphotericin B and staurosporine. Both laurinterol and (+)-elatol inhibited the adhesion of the N. fowleri trophozoites to the main proteins of the ECM when treating them at different concentrations and exposure times. This work not only reinforces the therapeutic potential of laurinterol and (+)-elatol against N. fowleri infection but also introduces the application of ECM-based adhesion assays as a novel and valuable tool for screening candidate compounds that disrupt host-pathogen interactions critical to PAM pathogenesis.
Insights
Two compounds, laurinterol and (+)-elatol, effectively inhibited the adhesion of Naegleria fowleri (N. fowleri) to extracellular matrix proteins. This finding highlights their therapeutic potential for treating primary amoebic meningoencephalitis (PAM).
Area of Science:
- Microbiology
- Parasitology
- Drug Discovery
Background:
- Primary amoebic meningoencephalitis (PAM) is a severe central nervous system infection caused by Naegleria fowleri.
- Naegleria fowleri adhesion to extracellular matrix (ECM) proteins is crucial for infection establishment.
- Targeting host-pathogen interactions offers a potential strategy for PAM prevention and treatment.
Purpose of the Study:
- To evaluate the anti-adhesion activity of laurinterol and (+)-elatol against Naegleria fowleri.
- To assess the efficacy of these compounds using an in vitro ECM-based adhesion model.
- To compare their effects with established drugs like amphotericin B and staurosporine.
Main Methods:
- In vitro ECM-based adhesion assay was employed.
- Naegleria fowleri trophozoites were exposed to varying concentrations and durations of laurinterol and (+)-elatol.
- Adhesion inhibition was quantified and compared to control groups and reference drugs.
Main Results:
- Both laurinterol and (+)-elatol demonstrated significant inhibition of N. fowleri trophozoite adhesion to ECM proteins.
- The inhibitory effect was concentration- and time-dependent.
- These sesquiterpenes showed promising anti-adhesion properties against N. fowleri.
Conclusions:
- Laurinterol and (+)-elatol exhibit therapeutic potential for combating N. fowleri infections.
- ECM-based adhesion assays are valuable tools for screening anti-PAM drug candidates.
- Disrupting N. fowleri adhesion to ECM is a viable strategy for developing novel PAM treatments.
