Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae

ABSTRACT The human-pathogenic fungus Aspergillus fumigatus is a ubiquitous saprophyte that causes fatal lung infections in immunocompromised individuals. Following inhalation, conidia are ingested by innate immune cells and can arrest phagolysosome maturation. How this virulence trait could have bee...

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Autores principales:	Iuliia Ferling, Joe Dan Dunn, Alexander Ferling, Thierry Soldati, Falk Hillmann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Aspergillus fumigatus Dictyostelium discoideum Protostelium aurantium DHN-melanin phagocytosis phagosome maturation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c29715319d5e41c79bc424f8f9fee853
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spelling	oai:doaj.org-article:c29715319d5e41c79bc424f8f9fee8532021-11-15T15:56:46ZConidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae10.1128/mBio.00862-202150-7511https://doaj.org/article/c29715319d5e41c79bc424f8f9fee8532020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00862-20https://doaj.org/toc/2150-7511ABSTRACT The human-pathogenic fungus Aspergillus fumigatus is a ubiquitous saprophyte that causes fatal lung infections in immunocompromised individuals. Following inhalation, conidia are ingested by innate immune cells and can arrest phagolysosome maturation. How this virulence trait could have been selected for in natural environments is unknown. Here, we found that surface exposure of the green pigment 1,8-dihydroxynaphthalene-(DHN)-melanin can protect conidia from phagocytic uptake and intracellular killing by the fungivorous amoeba Protostelium aurantium and delays its exocytosis from the nonfungivorous species Dictyostelium discoideum. To elucidate the antiphagocytic properties of the surface pigment, we followed the antagonistic interactions of A. fumigatus conidia with the amoebae in real time. For both amoebae, conidia covered with DHN-melanin were internalized at far lower rates than were seen with conidia lacking the pigment, despite high rates of initial attachment to nonkilling D. discoideum. When ingested by D. discoideum, the formation of nascent phagosomes was followed by transient acidification of phagolysosomes, their subsequent neutralization, and, finally, exocytosis of the conidia. While the cycle was completed in less than 1 h for unpigmented conidia, the process was significantly prolonged for conidia covered with DHN-melanin, leading to an extended intracellular residence time. At later stages of this cellular infection, pigmented conidia induced enhanced damage to phagolysosomes and infected amoebae failed to recruit the ESCRT (endosomal sorting complex required for transport) membrane repair machinery or the canonical autophagy pathway to defend against the pathogen, thus promoting prolonged intracellular persistence in the host cell and the establishment of a germination niche in this environmental phagocyte. IMPORTANCE Infections with Aspergillus fumigatus are usually acquired by an inhalation of spores from environmental sources. How spores of a saprophytic fungus have acquired abilities to withstand and escape the phagocytic attacks of innate immune cells is not understood. The fungal surface pigment dihydroxynaphtalene-melanin has been shown to be a crucial factor for the delay in phagosome maturation. Here, we show that this pigment also has a protective function against environmental phagocytes. Pigmented conidia escaped uptake and killing by the fungus-eating amoeba Protostelium aurantium. When ingested by the nonfungivorous phagocyte Dictyostelium discoideum, the pigment attenuated the launch of cell autonomous defenses against the fungal invader, such as membrane repair and autophagy, leading to prolonged intracellular retention. Membrane damage and cytoplasmic leakage may result in an influx of nutrients and thus may further promote intracellular germination of the fungus, indicating that A. fumigatus has acquired some of the basic properties of intracellular pathogens.Iuliia FerlingJoe Dan DunnAlexander FerlingThierry SoldatiFalk HillmannAmerican Society for MicrobiologyarticleAspergillus fumigatusDictyostelium discoideumProtostelium aurantiumDHN-melaninphagocytosisphagosome maturationMicrobiologyQR1-502ENmBio, Vol 11, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Aspergillus fumigatus Dictyostelium discoideum Protostelium aurantium DHN-melanin phagocytosis phagosome maturation Microbiology QR1-502
spellingShingle	Aspergillus fumigatus Dictyostelium discoideum Protostelium aurantium DHN-melanin phagocytosis phagosome maturation Microbiology QR1-502 Iuliia Ferling Joe Dan Dunn Alexander Ferling Thierry Soldati Falk Hillmann Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae
description	ABSTRACT The human-pathogenic fungus Aspergillus fumigatus is a ubiquitous saprophyte that causes fatal lung infections in immunocompromised individuals. Following inhalation, conidia are ingested by innate immune cells and can arrest phagolysosome maturation. How this virulence trait could have been selected for in natural environments is unknown. Here, we found that surface exposure of the green pigment 1,8-dihydroxynaphthalene-(DHN)-melanin can protect conidia from phagocytic uptake and intracellular killing by the fungivorous amoeba Protostelium aurantium and delays its exocytosis from the nonfungivorous species Dictyostelium discoideum. To elucidate the antiphagocytic properties of the surface pigment, we followed the antagonistic interactions of A. fumigatus conidia with the amoebae in real time. For both amoebae, conidia covered with DHN-melanin were internalized at far lower rates than were seen with conidia lacking the pigment, despite high rates of initial attachment to nonkilling D. discoideum. When ingested by D. discoideum, the formation of nascent phagosomes was followed by transient acidification of phagolysosomes, their subsequent neutralization, and, finally, exocytosis of the conidia. While the cycle was completed in less than 1 h for unpigmented conidia, the process was significantly prolonged for conidia covered with DHN-melanin, leading to an extended intracellular residence time. At later stages of this cellular infection, pigmented conidia induced enhanced damage to phagolysosomes and infected amoebae failed to recruit the ESCRT (endosomal sorting complex required for transport) membrane repair machinery or the canonical autophagy pathway to defend against the pathogen, thus promoting prolonged intracellular persistence in the host cell and the establishment of a germination niche in this environmental phagocyte. IMPORTANCE Infections with Aspergillus fumigatus are usually acquired by an inhalation of spores from environmental sources. How spores of a saprophytic fungus have acquired abilities to withstand and escape the phagocytic attacks of innate immune cells is not understood. The fungal surface pigment dihydroxynaphtalene-melanin has been shown to be a crucial factor for the delay in phagosome maturation. Here, we show that this pigment also has a protective function against environmental phagocytes. Pigmented conidia escaped uptake and killing by the fungus-eating amoeba Protostelium aurantium. When ingested by the nonfungivorous phagocyte Dictyostelium discoideum, the pigment attenuated the launch of cell autonomous defenses against the fungal invader, such as membrane repair and autophagy, leading to prolonged intracellular retention. Membrane damage and cytoplasmic leakage may result in an influx of nutrients and thus may further promote intracellular germination of the fungus, indicating that A. fumigatus has acquired some of the basic properties of intracellular pathogens.
format	article
author	Iuliia Ferling Joe Dan Dunn Alexander Ferling Thierry Soldati Falk Hillmann
author_facet	Iuliia Ferling Joe Dan Dunn Alexander Ferling Thierry Soldati Falk Hillmann
author_sort	Iuliia Ferling
title	Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae
title_short	Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae
title_full	Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae
title_fullStr	Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae
title_full_unstemmed	Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae
title_sort	conidial melanin of the human-pathogenic fungus <named-content content-type="genus-species">aspergillus fumigatus</named-content> disrupts cell autonomous defenses in amoebae
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/c29715319d5e41c79bc424f8f9fee853
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Conidial Melanin of the Human-Pathogenic Fungus <named-content content-type="genus-species">Aspergillus fumigatus</named-content> Disrupts Cell Autonomous Defenses in Amoebae

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