All you need is fungi: Exploring secondary metabolites as a source of novel amoebicidal agents

Free-living amoebae (FLAs) of the genus Acanthamoeba are opportunistic protozoa found in diverse environments. They can cause granulomatous amoebic encephalitis, especially in immunocompromised individuals, and Acanthamoeba keratitis, a painful corneal infection frequently associated with contact lens wearers. Effective treatments for Acanthamoeba infections are limited, with nitroimidazoles as the main pharmacological option, a class of drugs generally associated with side effects. Given the limited availability of vaccines and the low efficacy of existing drugs, the search for new therapeutic strategies is crucial. Interactions between fungi and predatory amoebae have driven the production of defensive fungal secondary metabolites (SMs) with potent amoebicidal properties. The evolutionary pressure from predatory amoebae has equipped fungi, particularly from the Aspergillus, Beauveria, and Fusarium genera, to produce a wide variety of defensive bioactive compounds, including non-ribosomal peptides, polyketides, and terpenes. Some examples of fungal-derived SMs include cephalosporins, mycophenolic acid, griseofulvin, pleuromutilins and lovastatin. Furthermore, gliotoxin and trypacidin from Aspergillus fumigatus exhibit amoebicidal activity by impairing key protozoan functions like phagocytosis. These findings highlight the potential of fungal SMs as novel amoebicidal agents. Exploring fungal biodiversity could lead to the discovery of innovative medicines, harnessing natural compounds to combat infections caused by Acanthamoeba species and other protozoan pathogens.