“Feast-Fit-Fist-Feat”: Overview of Free-living Amoeba Interactions with Fungi and Virulence as a Foundation for Success in Battle

Purpose of Review Free-living amoebae (FLAs) are ubiquitous and can co-habit similar niches and interact with fungi. Herein, we discuss theories on FLAs and the origin, evolution, and conservation of fungal virulence, proposing the “feast-fit-fist-feat” hypothesis that covers the knowledge on FLA-fungi interactions, and could be extended during evolutionarily host escalation. Overall, by bridling this selective pressure, fungi might return to environment and by serendipity, infect superior hosts. The selected traits might grant the fungus with an enhanced capacity to cause damage, or virulence. The fungal virulence factors that might be expressed during infection to amoeba and that grant a fungal benefit during infection to mammals are discussed. However, how they are induced during infection of FLAs is still an open field. Here we discuss also the “Trojan Horse” role of FLAs and the importance of co-infections and disease outcome. Recent Findings Herein, we discuss also at the molecular level the early steps on how FLAs are able to attach and internalize fungal pathogens. Upon entrance, amoeba interaction might pose selective pressures, and the result is usually a more virulent phenotype of the fungus. Amoeba is able to modulate several fungal virulence factors, most of them with relative importance for infection to superior or more evolved hosts. This interaction fungi-FLAs makes an attractive model for the application of the “One Health” concept in order to avoid new emerging more virulent fungal species. Summary Amoeba-fungi interactions are still an open field, with several avenues yet to be explored, which might explain the origin of microbial virulence and innate immunity evolution. Several mechanisms of direct or indirect regulation might be involved.