Maynooth University researchers have used mass spectrometry infrastructure, funded by Research Ireland, to collaborate on an important breakthrough on a serious but neglected tropical disease, mycetoma.
Mycetoma causes serious health problems for infected individuals living in low to middle income countries and is endemic in tropical and subtropical environments. Surgery and, in advanced cases, amputations are often necessary to resolve the infection.
Maynooth University Professor Sean Doyle of the Department of Biology and scientific researcher Cathal Murphy worked with teams from the Netherlands, Japan and Sudan to investigate the chronic skin infection. Their findings, published today in Nature Communications, are an important milestone in the study of the disease.
It is caused by the fungus Madurella mycetomatis, which forms black grains inside the tissue of mycetoma patients that protects it from both the immune system and antifungal agents given to treat this infection.
The research, led by Associate Prof Wendy van de Sande of the Erasmus Medical Centre in the Netherlands and Specially Appointed Prof Imad Abugessaisa of Osaka University and RIKEN IMS in Japan, established the importance of iron to the virulence and disease-causing potential of Madurella mycetomatis.
“It shows how investment in state-of-the-art facilities in Ireland can increase the opportunities for international collaboration and help contribute to the global recognition of Maynooth University as a centre of excellence for competitive life science research.”
In 2024, Maynooth University was awarded nearly €1.8 million by Research Ireland to fund high sensitivity liquid chromatography-mass spectrometry to enable detection and enumeration of biomolecules in a high-throughput and efficient manner.
In the study, the consortium made use of an invertebrate animal model, Galleria mellonella, in which they could follow grain formation over time. By performing RNA analysis on different time points, they were able to show that control of iron levels (iron homeostasis) in both the host and pathogen play an important role in mycetoma grain formation.
The consortium showed that M. mycetomatis produced siderophores, fungal molecules which are excreted to bring back iron to the fungal cell. Furthermore, the amount of iron within the host seemed to be important to either contain the fungus inside the grain or to actively grow further outside the grain. Therefore, interfering with the iron uptake might be a promising target for drug discovery.
The MU researchers played a contributing role by enabling the team to isolate and identify these siderophores, the iron-binding peptides produced by M. mycetomatis.
Read the full study here.