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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Published in:Nature communications Vol. 16; no. 1; pp. 5324 - 18
Main Authors: 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
Language:English
Published: London Nature Publishing Group UK 25.06.2025
Nature Publishing Group
Nature Portfolio
Subjects:
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 Access:Get full text
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Summary: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.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-025-60875-2