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Scientific article
Open access
English

Conidial Melanin of the Human-Pathogenic Fungus"Aspergillus fumigatus" Disrupts Cell Autonomous Defenses in Amoebae

Published inmBio, vol. 11, no. 3
Publication date2020
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.

Keywords
  • Aspergillus fumigatus
  • Dictyostelium discoideum
  • Protostelium aurantium
  • DHN-melanin
  • Phagocytosis
  • Phagosome maturation
  • Acidification
  • V-ATPase
  • ROS
  • NADPH oxidase
  • Membrane damage
  • Membrane repair
  • ESCRT machinery
  • Fungi
  • Amoeba
  • Pathogens
Citation (ISO format)
FERLING, Iuliia et al. Conidial Melanin of the Human-Pathogenic Fungus’Aspergillus fumigatus’ Disrupts Cell Autonomous Defenses in Amoebae. In: mBio, 2020, vol. 11, n° 3. doi: 10.1128/mBio.00862-20
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Article (Published version)
accessLevelPublic
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ISSN of the journal2150-7511
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186downloads

Technical informations

Creation09/07/2020 10:30:00 AM
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Update time03/15/2023 10:31:23 PM
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