June 25, 2025 by Premium Research Institute for Human Metaverse Medicine (PRIMe) edited by Sadie Harley , reviewed by Robert Egan scientific editor associate editor This article has been reviewed according to Science X's editorial process and policies . Editors have highlightedthe following attributes while ensuring the content's credibility: fact-checked peer-reviewed publication proofread A groundbreaking study led by a global research consortium offers renewed hope for patients battling mycetoma, a neglected tropical disease. Researchers utilized an insect model – Galleria mellonella – coupled with comprehensive transcriptome analysis to unravel the intricate mechanisms governing iron regulation between host tissue and the mycetoma grain, a characteristic fungal mass central to the disease. The research, published in the prestigious journal *Nature Communications*, illuminates how the causative fungus strategically invades and establishes these protective grains within subcutaneous tissue, significantly paving the way for the development of novel drug therapies and less invasive treatment strategies, potentially dramatically reducing the patient burden. Mycetoma, a chronic and debilitating infectious disease predominantly affecting impoverished communities, is characterized by the insidious development of black grains within infected tissue. These grains serve as a formidable shield, protecting the causative fungus from both the host’s immune system and conventional antifungal agents, presenting a major obstacle to effective treatment and often necessitating surgery or even amputation. Until now, the precise process of grain formation remained largely shrouded in mystery. This extensive study, spearheaded by Special Appointed Professor Imad Abugessaisa (full time), in collaboration with Associate Professor Wendy van de Sande from Erasmus University Medical Center in the Netherlands, brought together a powerful consortium from RIKEN IMS (Japan), Erasmus MC (Netherlands), Maynooth University (Ireland), and the Mycetoma Research Center (WHO collaborating center on Mycetoma and Skin Neglected Tropical Diseases, Sudan). The team employed state-of-the-art histology techniques, advanced omics technologies, and sophisticated computational biology to meticulously dissect the formation and development of mycetoma grains. Notably, the consortium utilized the invertebrate model, *Galleria mellonella*, enabling them to track grain formation in real-time over extended periods. Through detailed RNA analysis conducted at various time points, the researchers demonstrated that iron homeostasis – the delicate balance of iron levels – plays a pivotal role in both the host and the pathogen during mycetoma grain development. The study’s findings represent a significant milestone within the field of mycetoma research, building upon early documentation of grain presence as far back as 1840. The research definitively answers the long-standing question of how these grains form and which processes, both in the host and the pathogen, contribute to their development. A key discovery revealed that the primary mycetoma causative agent produces siderophores – specialized fungal molecules secreted to scavenge iron and actively return it to the fungal cell. Furthermore, the availability of iron within the host tissue appears to be a critical factor, either containing the fungus within the grain or fueling its active growth outside of it. This understanding suggests that interfering with iron uptake could represent a promising target for future drug discovery efforts.

Reflecting on this transformative achievement, Professor Imad Abugessaisa stated, "In Wad Onsa, Sudan, a village with the world’s highest prevalence of mycetoma – where the disease leaves many disabled and impoverished, especially young people – I was determined to make a difference. Partnering with Dr. Wendy van de Sande, we embarked on this research." This publication underscores the paramount importance of collaboration in achieving scientific breakthroughs and directly addressing critical societal needs. Further details can be found in the article: "Iron regulatory pathways differentially expressed during *Madurella mycetomatis* grain development in *Galleria mellonella*,” *Nature Communications* (2025). DOI: 10.1038/s41467-025-60875-2. Journal information: *Nature Communications*. Provided by Premium Research Institute for Human Metaverse Medicine (PRIMe).