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Exploring Virulence Determinants of Filamentous Fungal Pathogens through Interactions with Soil Amoebae
Silvia Novohradská1,2, Iuliia Ferling1,2, Falk Hillmann1
1Evolution of Microbial Interactions, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.
Abstract:
Infections with filamentous fungi are common to all animals, but attention is rising especially due to the increasing incidence and high mortality rates observed in immunocompromised human individuals. Here, Aspergillus fumigatus and other members of its genus are the leading causative agents. Attributes like their saprophytic life-style in various ecological niches coupled with nutritional flexibility and a broad host range have fostered the hypothesis that environmental predators could have been the actual target for some of their virulence determinants. In this mini review, we have merged the recent findings focused on the potential dual-use of fungal defense strategies against innate immune cells and soil amoebae as natural phagocytes. Well-established virulence attributes like the melanized surface of fungal conidia or their capacity to produce toxic secondary metabolites have also been found to be protective against the model amoeba Dictyostelium discoideum. Some of the recent advances during interaction studies with human cells have further promoted the adaptation of other amoeba infection models, including the wide-spread generalist Acanthamoeba castellanii, or less prominent representatives like Vermamoeba vermiformis. We further highlight prospects and limits of these natural phagocyte models with regard to the infection biology of filamentous fungi and in comparison to the phagocytes of the innate immune system.
Insights
Filamentous fungi, like Aspergillus, cause severe infections in immunocompromised individuals. Their defense mechanisms, evolved against soil amoebae, may also target human immune cells, offering new insights into fungal virulence.
Area of Science:
- Mycology
- Immunology
- Evolutionary Biology
Background:
- Filamentous fungi, particularly Aspergillus species, are significant causes of infection, especially in immunocompromised populations.
- Fungal virulence factors may have evolved to target environmental predators, such as soil amoebae.
- Understanding fungal-host interactions is crucial due to rising infection rates and mortality.
Purpose of the Study:
- To review recent findings on fungal defense strategies against both soil amoebae and human innate immune cells.
- To explore the hypothesis of dual-use virulence determinants in filamentous fungi.
- To assess the utility of amoeba models in studying fungal infection biology.
Main Methods:
- Literature review of recent findings on fungal-amoebae and fungal-human cell interactions.
- Analysis of established fungal virulence attributes, including melanized surfaces and secondary metabolites.
- Comparison of different amoeba models (e.g., Dictyostelium discoideum, Acanthamoeba castellanii, Vermamoeba vermiformis) for studying fungal infections.
Main Results:
- Fungal virulence factors, such as melanized conidia and toxic metabolites, protect against amoebae like Dictyostelium discoideum.
- Amoeba models are increasingly used to study fungal interactions, complementing studies with human cells.
- Specific amoeba species like Acanthamoeba castellanii and Vermamoeba vermiformis are being adapted for these studies.
Conclusions:
- Fungal defense strategies against natural phagocytes (amoebae) may represent a conserved mechanism that also impacts human innate immunity.
- Amoeba models offer valuable insights into the infection biology of filamentous fungi, complementing traditional host-pathogen studies.
- Further research using these models can elucidate fungal virulence and inform therapeutic strategies against invasive fungal infections.
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