Proteomics

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Proteomic analysis of the processes leading to Madurella mycetomatis grain formation in Galleria mellonella larvae


ABSTRACT: 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.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Galleria Mellonella Madurella Mycetomatis

SUBMITTER: Gerard Sheehan  

LAB HEAD: Kevin Kavanagh

PROVIDER: PXD013532 | Pride | 2020-03-19

REPOSITORIES: Pride

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Publications

Proteomic analysis of the processes leading to Madurella mycetomatis grain formation in Galleria mellonella larvae.

Sheehan Gerard G   Konings Mickey M   Lim Wilson W   Fahal Ahmed A   Kavanagh Kevin K   van de Sande Wendy W J WWJ  

PLoS neglected tropical diseases 20200408 4


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, prot  ...[more]

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