{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:34:48Z","timestamp":1790678088241,"version":"4.1.0"},"reference-count":43,"publisher":"National Academy of Sciences","issue":"27","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,7,8]]},"abstract":"\n Zygomycosis is an emerging frequently fatal opportunistic mycosis whose immunopathogenesis is poorly understood. We developed a zygomycosis model by injecting\n Drosophila melanogaster<\/jats:italic>\n flies with a standardized amount of fungal spores from clinical Zygomycetes isolates to study virulence and host defense mechanisms. We found that, as opposed to most other fungi, which are nonpathogenic in\n D. melanogaster<\/jats:italic>\n (e.g.,\n Aspergillus fumigatus<\/jats:italic>\n ), Zygomycetes rapidly infect and kill wild-type flies\n . Toll<\/jats:italic>\n -deficient flies exhibited increased susceptibility to Zygomycetes, whereas constitutive overexpression of the antifungal peptide\n Drosomycin<\/jats:italic>\n in transgenic flies partially restored resistance to zygomycosis.\n D. melanogaster<\/jats:italic>\n Schneider 2 phagocytic cells displayed decreased phagocytosis and caused less hyphal damage to Zygomycetes compared with that to\n A. fumigatus<\/jats:italic>\n . Furthermore, phagocytosis-defective\n eater<\/jats:italic>\n mutant flies displayed increased susceptibility to Zygomycetes infection. Classic enhancers of Zygomycetes virulence in humans, such as corticosteroids, increased iron supply, and iron availability through treatment with deferoxamine dramatically increased Zygomycetes pathogenicity in our model. In contrast, iron starvation induced by treatment with the iron chelator deferasirox significantly protected flies infected with Zygomycetes. Whole-genome expression profiling in wild-type flies after infection with Zygomycetes vs.\n A. fumigatus<\/jats:italic>\n identified genes selectively down-regulated by Zygomycetes, which act in pathogen recognition, immune defense, stress response, detoxification, steroid metabolism, or tissue repair or have unknown functions. Our results provide insights into the factors that mediate host\u2013pathogen interactions in zygomycosis and establish\n D. melanogaster<\/jats:italic>\n as a promising model to study this important mycosis.\n <\/jats:p>","DOI":"10.1073\/pnas.0709578105","type":"journal-article","created":{"date-parts":[[2008,6,26]],"date-time":"2008-06-26T21:06:52Z","timestamp":1214514412000},"page":"9367-9372","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":133,"title":["Drosophila melanogaster<\/i>\n as a model host to dissect the immunopathogenesis of zygomycosis"],"prefix":"10.1073","volume":"105","author":[{"given":"Georgios","family":"Chamilos","sequence":"first","affiliation":[{"name":"Departments of *Infectious Diseases, Infection Control and Employee Health,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Departments of *Infectious Diseases, Infection Control and Employee Health,"},{"name":"College of Pharmacy, University of Houston, Houston, TX 77030"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Hu","sequence":"additional","affiliation":[{"name":"Bioinformatics, and Computational Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianchun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Bioinformatics, and Computational Biology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Zal","sequence":"additional","affiliation":[{"name":"Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Gilliet","sequence":"additional","affiliation":[{"name":"Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Halder","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology, University of Texas M. 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Anderson Cancer Center, Houston, TX 77030; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios P.","family":"Kontoyiannis","sequence":"additional","affiliation":[{"name":"Departments of *Infectious Diseases, Infection Control and Employee Health,"},{"name":"College of Pharmacy, University of Houston, Houston, TX 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