부산대학교 도서관

Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Characteristic of this infection is the formation of grains. However, the processes leading to grain formation are not known. In this study, we employed a proteomic approach to characterise M. mycetomatis grain formation in Galleria mellonella larvae and map the processes leading to grain formation over time. For this, at 1 day, 3 days and 7 days post-inoculation, proteins from grains and hemolymph were extracted and analysed by label-free mass spectrometry. A total of 87, 51 and 48 M. mycetomatis proteins and 713, 997, 18 G. mellonella proteins were found in grains on day 1, 3 and 7 post-inoculation respectively. M. mycetomatis proteins were mainly involved in cellular metabolic processes and numerous enzymes were encountered. G. mellonella proteins were primarily involved in the nodulation process. The proteins identified were linked to nodulation and grain formation and four steps of grain formation were identified. The results of this proteomic approach could in the future be used to design novel strategies to interfere with mycetoma grain formation and to combat this difficult to treat infection. Author summary: Although grain formation is the hallmark of mycetoma, so far the pathways leading to grain formation were not studied. Since our hypothesis is that both host and pathogen play a role in this process, we aimed to study this process in a model system. Grains can be formed in the invertebrate Galleria mellonella and different stages of grain formation can be noted within the larvae. We therefore infected G. mellonella with the mycetoma causative agent Madurella mycetomatis, and monitored grain formation over time. At day 1, day 3 and day 7 post-inoculation, grains and hemolymph were obtained from infected larvae. Proteins were isolated and identified by label-free mass spectrometry. By analyzing the proteins found in both host and pathogen on the different time points, we were able to develop a grain model over time. This grain model can in the future be used to identify novel treatments for this difficult to treat infection. [ABSTRACT FROM AUTHOR]