Iron regulatory pathways differentially expressed during Madurella mycetomatis grain development in Galleria mellonella

Mycetoma is a chronic granulomatous infection of the subcutaneous tissue, most often caused by the fungal pathogen Madurella mycetomatis . Characteristic of the infection is the formation of grains. However, knowledge of the function and formation of the grain is limited. Here, we use a Galleria mel...

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Veröffentlicht in:	Nature communications Jg. 16; H. 1; S. 5324 - 18
Hauptverfasser:	Abugessaisa, Imad, Konings, Mickey, Manabe, Ri-Ichiroh, Murphy, Cathal M., Kawashima, Tsugumi, Hasegawa, Akira, Takahashi, Chitose, Tagami, Michihira, Okazaki, Yasushi, Eadie, Kimberly, Lim, Wilson, Doyle, Sean, Verbon, Annelies, Fahal, Ahmed H., Kasukawa, Takeya, van de Sande, Wendy W. J.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 25.06.2025 Nature Publishing Group Nature Portfolio
Schlagworte:	101/47 38/39 38/91 631/326/193 631/326/193/2542 631/326/193/2544 82/58 Animals Biosynthesis Cement Chronic infection Ferritin Ferritins - genetics Ferritins - metabolism Fungal diseases Fungal Proteins - genetics Fungal Proteins - metabolism Fungi Galleria mellonella Gene Expression Profiling Gene Expression Regulation, Fungal Genes Genomes Grain size Humanities and Social Sciences Infections Inoculation Insects Iron Iron - metabolism Larva - metabolism Larva - microbiology Larvae Madurella - genetics Madurella - growth & development Madurella - metabolism Madurella mycetomatis Moths - microbiology multidisciplinary Mycetoma - metabolism Mycetoma - microbiology Pathogens Protein transport Science Science (multidisciplinary) Tandem Mass Spectrometry Transcriptome Transcriptomics Transferrin Transferrin - genetics Transferrin - metabolism
ISSN:	2041-1723, 2041-1723
Online-Zugang:	Volltext
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Zusammenfassung:	Mycetoma is a chronic granulomatous infection of the subcutaneous tissue, most often caused by the fungal pathogen Madurella mycetomatis . Characteristic of the infection is the formation of grains. However, knowledge of the function and formation of the grain is limited. Here, we use a Galleria mellonella larvae infection model and transcriptomic profiling to identify processes associated with M. mycetomatis grain formation. Larvae were infected with M. mycetomatis and, after 4, 24, 72 and 168 h post-inoculation, RNA was extracted from larval content and sequenced. We found that 3498 G. mellonella and 136 M. mycetomatis genes were differentially expressed during infection. In particular, genes encoding proteins related to iron transport were highly expressed by both G. mellonella (transferrin and ferritin) and M. mycetomatis (SidA, SidD and SidI). LC-MS/MS analysis of M. mycetomatis cultured under iron-limiting conditions revealed the presence of SidA and SidD orthologs, and concurrent RP-HPLC and LC-MS identified a singly charged, putative siderophore in culture supernatant. Furthermore, we show that M. mycetomatis can obtain iron from holoferritin. Thus, our results highlight the importance of iron acquisition pathways during grain formation, suggesting potential avenues for development of new diagnostic and therapeutic strategies for mycetoma. Mycetoma is a chronic granulomatous infection of the subcutaneous tissue, most often caused by the fungal pathogen Madurella mycetomatis . Here, the authors show that iron acquisition pathways in both pathogen and host are upregulated during grain formation in an insect larva infection model.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-025-60875-2