The fungivorous amoeba Protostelium aurantium targets redox homeostasis and cell wall integrity during intracellular killing of Candida parapsilosis.

Radosa S, Sprague JL, Lau SH, Tóth R, Linde J, Krüger T, Sprenger M, Kasper L, Westermann M, Kniemeyer O, Hube B, Brakhage AA, Gácser A, Hillmann F (2021) The fungivorous amoeba Protostelium aurantium targets redox homeostasis and cell wall integrity during intracellular killing of Candida parapsilosis. Cell Microbiol , e13389.

Abstract

Predatory interactions among microbes are a major evolutionary driving force for biodiversity. The fungivorous amoeba Protostelium aurantium has a wide fungal food spectrum including foremost pathogenic members of the genus Candida. Here we show that upon phagocytic ingestion by the amoeba, C. parapsilosis is confronted with an oxidative burst and undergoes lysis within minutes of processing in acidified phagolysosomes. On the fungal side, a functional genomic approach identified copper and redox homeostasis as primary targets of amoeba predation, with the highly expressed copper exporter gene CRP1 and the peroxiredoxin gene PRX1 contributing to survival when encountered with P. aurantium. The fungicidal activity was largely retained in intracellular vesicles of the amoebae. Following their isolation, the content of these vesicles induced immediate killing and lysis of C. parapsilosis in vitro. Proteomic analysis identified 56 vesicular proteins from P. aurantium. Although completely unknown proteins were dominant, many of them could be categorized as hydrolytic enzymes targeting the fungal cell wall, indicating that fungal cell wall structures are under selection pressure by predatory phagocytes in natural environments. This article is protected by copyright. All rights reserved.

Leibniz-HKI-Authors

Axel A. Brakhage
Falk Hillmann
Olaf Kniemeyer
Thomas Krüger
Bernhard Hube
Lydia Kasper
Silvia Radosa
Marcel Sprenger
Jakob Sprague
Siu Hin Lau

Awards

Cover Picture, Editors choice

Identifier

doi: 10.1111/cmi.13389

PMID: 34460149