Dataset Information

The acute host – pathogen interactions between Aspergillus fumigatus and Galleria mellonella

ABSTRACT: Larvae of the greater wax moth Galleria mellonella are an ideal in vivo model to quickly and easily assess the virulence of a range of human pathogens, to comprehensively analyse the host – pathogen interactome and to reproducibly evaluate the in vivo toxicity and efficacy of anti-microbial agents. G. mellonella larvae are easy to inoculate, generate results within 48 hours and are free from the ethical and legal restrictions which surround the use of mammals for this type of testing.1,2 Microbial virulence and pathogenesis can be assessed by a variety of endpoints including survival, fluctuations in hemocyte density, oscillations in fungal burden and changes in hemolymph proteome. Insect hemocytes can be easily isolated and used in ex vivo cellular assays to determine phagocyte – pathogen interactions. Aspergillus fumigatus infection and dissimiation as well as G. mellonella cellular and humoral immune responses were analysed over 24 hours.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Galleria Mellonella

TISSUE(S): Blood

SUBMITTER: Gerard Sheehan

LAB HEAD: Kevin Kavanagh

PROVIDER: PXD008196 | Pride | 2018-06-21

REPOSITORIES: Pride

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Publications

Characterisation of the cellular and proteomic response of Galleria mellonella larvae to the development of invasive aspergillosis.

Sheehan Gerard G Clarke Gráinne G Kavanagh Kevin K

BMC microbiology 20180628 1

<h4>Background</h4>Galleria mellonella larvae were infected with conidia of Aspergillus fumigatus and the cellular and humoral immune responses of larvae to the pathogen were characterized as invasive aspergillosis developed.<h4>Results</h4>At 2 h post-infection there was an increase in hemocyte density to 7.43 ± 0.50 × 10<sup>6</sup>/ml from 0.98 ± 0.08 × 10<sup>6</sup>/ml at 0 h. Hemocytes from larvae immune primed for 6 h with heat killed A. fumigatus conidia displayed superior anti-fungal ac ...[more]

PMID: 29954319

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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.

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