Amoebae as evolutionary models for fungal virulence and phagocytic processing
1Independent Junior Research Group – Evolution of Microbial Interactions, Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute, Jena, Germany
2Faculty of Engineering, Hochschule Wismar, University of Applied Sciences, Technology, Business and Design, Wismar, Germany
Free living amoebae share striking similarities with innate immune cells in terms of cell morphology, motility and phagocytic processing of microbes. Moreover, their abilities to ﬁnd ingest and kill microbes in their natural habitats have fostered the hypothesis that amoebae could have served as a training ground for environmentally acquired pathogens. What may have been more obvious for intracellular bacteria and fungi becomes increasingly clear also for several fungal pathogens: Here, I will show that a number of virulence determinants even from the genus Candida or the filamentous fungus Aspergillus fumigatus are equally relevant to resist innate immune cells and environmental phagocytic predators. We recently isolated the fungus specific predator Protostelium aurantium, an amoeba which is widespread in terrestrial habitats and feeds exclusively on fungi. The amoeba ingests and kills a wide range of fungal pathogens including several basidiomycetous yeast and members of the Candida clade. However, C. albicans and C. glabrata, were efficiently protected, either due to extensive mannoprotein coating of the cell surface or the use of short chain ubiquinone cofactors, respectively. When encountering fungal hyphae such as those of A. fumigatus, the amoeba switched from phagocytosis to ruphocytosis, meaning that the fungal hyphae were actively invaded, and the entire cytoplasm was resorbed within minutes. Phagocytic studies with immunologically inert conidia showed that the uptake of melanized conidia was generally avoided and led to prolonged intracellular retention, finally causing enhanced damage to the amoeba phagolysosomal membrane. Our results indicate that several known virulence attributes actually serve a dual role by providing protection against environmental predators and may be under significant selective pressure in natural habitats.
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