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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.
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.
