Dataset Information

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]

PMID: 32267851

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Project description:Polymicrobial infections are intrinsically less susceptible to antimicrobial therapy, are more invasive and can induce enhanced inflammatory responses leading to negative clinical outcomes. The importance of studying the interaction between microbes themselves and their interactions with their host in combination has only been realised in recent years. However, there is a lack of simple, effective and low cost in vivo models to study these interactions with the host immune response. This study details the responses of Galleria mellonella larvae to disseminated combination infection by C. albicans and S. aureus and demonstrates the efficacy of antimicrobial chemotherapy on treating co-infected larvae. Doses of C. albicans (1 × 105 larva-1) and S. aureus (1 × 104 larva-1) which were non-lethal in mono-infection, when combined significantly lowered larval survival at (70 ± 3.33% [p < 0.01]), 48 (10 ± 3.33% [p < 0.0001]) and 72h (5 ± 6.66% [p < 0.0001]) h relative to larvae receiving S. aureus 2 × 104 larva-1 mono-infection. Co-infected larvae with S. aureus 2 × 104 larva-1 resulted in an increase in the density of circulating hemocytes relative to S. aureus mono-infected larvae. Co-infected larvae displayed a significantly higher overall S. aureus c.f.u larva-1 compared to larvae only infected with S. aureus. Co-infection resulted in dissemination throughout the host and the appearance of large nodules. Proteomic analysis of co-infected larval hemolymph revealed specific immune responses to bacterial and fungal infection by the increased abundance of a range of antimicrobial peptides, peptidoglycan, lipopolysaccharide and β-glucan recognition proteins and proteins associated with tissue invasion and nodule formation. The in vitro and in vivo efficacy of empirical antimicrobial drugs (amphotericin B & meropenem) was examined against C. albicans and S. aureus was also examined. meropenem was more effective than amphotericin B but a combination was most effective at improving survival of co-infected larvae. The effect of antimicrobial therapy on symptoms associated with co-infection was also assessed using Cryo-imaging. The processes of polymicrobial co-infection in G. mellonella are compared to those in mice models and larvae provide an easy to use and ethically acceptable in vivo system to assess polymicrobial interactions with their host.

Dataset Information

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

Publications

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

Similar Datasets

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