Similar Datasets
Project description:Mycetoma is a neglected, 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. To map the processes leading to M. mycetomatis grain formation, we used a Galleria mellonella larvae infection model and time-course transcriptomic profiling. In the infected G. mellonella 88.0% of the RNA sequence reads mapped to G. mellonella, only 0.01% mapped to M. mycetomatis. Differential Gene Expression analysis revealed that 3.498 G. mellonella and 137 M. mycetomatis genes were differentially expressed during infection. Most of the enriched GO terms of both host and pathogen are linked to energy pathways, nucleobase metabolic process, and cation and iron transport. Genes related to iron transport were highly expressed by both G. mellonella (transferrin and ferritin) and M. mycetomatis (SidA, SidD and SidI). A protein-protein interaction network analysis of D. melanogaster homologues genes in M. mycetomatis revealed the expression of the entire siderophore biosynthesis pathway throughout infection. Many host and pathogen genes were differentially expressed during infection. The identification of the importance of iron acquisition during grain formation can be exploited as a potential novel diagnostic and therapeutic strategy for mycetoma.
2025-05-21 | GSE213332 | GEO
Project description:Mycetoma is a neglected, 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. To map the processes leading to M. mycetomatis grain formation, we used a Galleria mellonella larvae infection model and time-course transcriptomic profiling. In the infected G. mellonella 88.0% of the RNA sequence reads mapped to G. mellonella, only 0.01% mapped to M. mycetomatis. Differential Gene Expression analysis revealed that 3.498 G. mellonella and 137 M. mycetomatis genes were differentially expressed during infection. Most of the enriched GO terms of both host and pathogen are linked to energy pathways, nucleobase metabolic process, and cation and iron transport. Genes related to iron transport were highly expressed by both G. mellonella (transferrin and ferritin) and M. mycetomatis (SidA, SidD and SidI). A protein-protein interaction network analysis of D. melanogaster homologues genes in M. mycetomatis revealed the expression of the entire siderophore biosynthesis pathway throughout infection. Many host and pathogen genes were differentially expressed during infection. The identification of the importance of iron acquisition during grain formation can be exploited as a potential novel diagnostic and therapeutic strategy for mycetoma.
2025-05-21 | GSE213329 | GEO
Project description: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.
| S-EPMC7141616 | biostudies-literature
Project description: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. To map the processes leading to M. mycetomatis grain formation, we used a Galleria mellonella larvae infection model and transcriptomic profiling. G. mellonella larvae were infected with M. mycetomatis and after 4h, 24h, 72h and 168h post-inoculation, RNA was extracted from larval content and sequenced. Differential Gene Expression analysis revealed that 3,498 G. mellonella and 136 M. mycetomatis genes were differentially expressed during infection. Among these genes, genes 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. M. mycetomatis could also obtain iron from holoferritin. The identification of the importance of iron acquisition during grain formation can be exploited as a potential novel diagnostic and therapeutic strategy for mycetoma.
2025-05-15 | PXD063449 | Pride
Project description:Analysis of Madurella mycetomatis grain development in Galleria mellonella
| PRJNA880565 | ENA
Project description:Timecourse CAGE analysis of Madurella mycetomatis grain development in Galleria mellonella
| PRJNA880765 | ENA
Project description:Mycetoma is a neglected chronic and granulomatous infection primarily associated with the fungal pathogen Madurella mycetomatis. Infection is characterised by the formation of fungal grains inside the infected tissue which commonly result in severe deformity and disability. Currently the biochemical processes and interactions between host and pathogen which result in grain formation are unknown. Furthermore, the infection process in mammals takes months to fully develop. In order to unravel these processes Galleria mellonella larvae were infected with M. mycetomatis and hyphae and grain formation, survival, fungal burden and proteomic responses of larvae were monitored for 10 days. At 24 h post infection proteins indicative of muscle invasion and humoral immune response activation were enriched in infected larval hemolymph. By 72 h immune related hdd11 was increased 337 fold, heat shock proteins 90 was increased 40 fold and glutathione-S-transferase was increased 25 fold. By 7 days post infection proteins which were associated with grain formation (hdd11 [533 fold], hemocentin [54 fold]) and a range of antimicrobial peptides were enriched. During the 7 day period a variety of proteins were decreased in infected hemolymph (e.g. hexamerin, apolipophorin and cationic peptide CP8). This data also identified 75 M. mycetomatis proteins released into hemolymph during infection. Proteins were also extracted from M. mycetomatis grains taken from larvae infected for 24, 72 and 7 days. These proteins give an insight into the interactions between the larval immune response and M. mycetomatis at the cellular levels during infection. These results identify similarities between the infection processes of M. mycetomatis in G. mellonella larvae and in humans and identify novel proteins from M. mycetomatis which may play a crucial role in grain development.
2020-03-19 | PXD013532 | Pride
Project description:Eumycetoma is a neglected tropical disease, and Madurella mycetomatis, the most common causative agent of this disease forms black grains in hosts. Melanin was discovered to be one of the constituents in grains. Melanins are hydrophobic, macromolecular pigments formed by oxidative polymerisation of phenolic or indolic compounds. M. mycetomatis was previously known to produce DHN-melanin and pyomelanin in vitro. These melanin was also discovered to decrease M. mycetomatis's susceptibility to antifungals itraconazole and ketoconazole in vitro. These findings, however, have not been confirmed in vivo. To discover the melanin biosynthesis pathways used by M. mycetomatis in vivo and to determine if inhibiting melanin production would increase M. mycetomatis's susceptibility to itraconazole, inhibitors targeting DHN-, DOPA- and pyomelanin were used. Treatment with DHN-melanin inhibitors tricyclazole, carpropamid, fenoxanil and DOPA-melanin inhibitor glyphosate in M. mycetomatis infected Galleria mellonella larvae resulted in presence of non-melanized grains. Our finding suggested that M. mycetomatis is able to produce DOPA-melanin in vivo. Inhibiting DHN-melanin with carpropamid in combination with the antifungal itraconazole also significantly increased larvae survival. Our results suggested that combination treatment of antifungals and melanin inhibitors can be an alternative treatment strategy that can be further explored. Since the common black-grain eumycetoma causing agents uses similar melanin biosynthesis pathways, this strategy may be applied to them and other eumycetoma causative agents.Lay summaryMelanin protects fungi from environmental stress and antifungals. We have discovered that Madurella mycetomatis produces DHN-, pyomelanin and DOPA-melanin in vivo. Inhibiting M. mycetomatis DHN-melanin biosynthesis increases therapeutic value of the antifungal itraconazole in vivo.
| S-EPMC9295015 | biostudies-literature
Project description:Timecourse RNA-seq analysis of Madurella mycetomatis grain development in Galleria mellonella
| PRJNA880766 | ENA
Project description:Using Low Quantity single strand CAGE (LQ-ssCAGE) we mapped the transcription start sites (TSS) and annotated the 5' end of the invertebrate Galleria mellonella which is upcoming and booming in the last years as an experimental model in infection disease and immunology research. The current genome annotation of this model lacks the annotation of the 5' end and TSS information. To map TSS under healthy and infection conditions, the G. mellonella larva was infected with the fungal pathogen Madurella mycetomatis After 4, 30 and 52 hours of the infection, larvae were treated with itraconazole or ravuconazole. RNA-seq and LQ-ssCAGE libraries prepared and sequenced. The LQ-ssCAGE data was processed to identify CAGE transcription start site (CTSS), uni- and bi-directional clusters. LQ-ssCAGE enabled us to precisely identify (39,410) TSS and (249) active enhancers. We assigned genomic features to the resulting TSSs and enhancers. The majority of the TSS peaks are annotated as promoter regions while the enhancers were annotated as intergenic and genic. Furthermore, we confirmed the quality of TSS by promoter shapes and GC bias. We identified a set of super-enhancers and predicted de-novo motifs. In this study we reported the first atlas of TSS and active enhancers of the G. mellonella.
2024-12-11 | GSE282923 | GEO