Targeting of phagolysosomes containing conidia of the human pathogenic fungus Aspergillus fumigatus with polymeric particles.

González K*, Gangapurwala G*, Alex J*, Vollrath A, Cseresnyés Z, Weber C, Czaplewska JA, Hoeppener S, Svensson CM, Orasch T, Heinekamp T, Guerrero-Sánchez C, Figge MT, Schubert US, Brakhage AA (2022) Targeting of phagolysosomes containing conidia of the human pathogenic fungus Aspergillus fumigatus with polymeric particles. Appl Microbiol Biotechnol [Accepted]

*equal contribution

Abstract

Conidia of the airborne human-pathogenic fungus Aspergillus fumigatus are inhaled by humans. In the lung, they are phagocytosed by alveolar macrophages and intracellularly processed. In macrophages, however, conidia can interfere with the maturation of phagolysosomes to avoid their elimination. To investigate, whether polymeric particles (PPs) can reach this intracellular pathogen in macrophages, we formulated dye-labeled PPs with a size allowing for their phagocytosis. PPs were efficiently taken up by RAW 264.7 macrophages and were found in phagolysosomes. When macrophages were infected with conidia prior to the addition of PPs we found that they co-localized in the same phagolysosomes. Mechanistically, fusion of phagolysosomes containing PPs with phagolysosomes containing conidia was observed. Increasing concentrations of PPs increased fusion events resulting in 14% of phagolysosomes containing both conidia and PPs. We demonstrate that PPs can reach conidia-containing phagolysosomes making these particles a promising carrier system for antimicrobial drugs to target intracellular pathogens.

Leibniz-HKI-Authors

Axel A. Brakhage
Zoltán Cseresnyés
Marc Thilo Figge
Katherine Gonzalez Rojas
Thorsten Heinekamp
Thomas Orasch
Carl-Magnus Svensson