Dataset Information

Proteomic responses of Candida albicans to Galleria mellonella larvae hemolymph

ABSTRACT: This study assessed the development of disseminated candidiasis within Galleria mellonella larvae and characterised the proteomic responses of Candida albicans to larval hemolymph. Infection of larvae with an inoculum of 1 × 106 yeast cell reduced larval viability 24 (53.33 ± 3.33%), 48 (33.33 ± 3.33%) and 72 (6.66 ± 3.33%) hour post infection. C. albicans infection quickly disseminated from the site of inoculation and the presence of yeast and hyphal forms were found in nodules extracted from infected larvae at 6 and 24 hours. A range of proteins secreted during infection of G. mellonella were detected in larval hemolymph and these were enriched for biological processes such as interaction with host and pathogenesis. The candicidal activity of hemolymph after immediate incubation of yeast cells resulted in a decrease in yeast cell viability (0.23 ± 0.03 × 106, p < 0.05) as compared to control (0.99 ± 0.01 × 106). extracellular (in vivo) proteome of C. albicans in larval hemolymph were assessed. C. albicans responds to incubation in hemolymph ex vivo by the induction of an oxidative stress response, a decrease in proteins associated with protein synthesis and an increase in glycolytic proteins.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Candida Albicans (yeast)

SUBMITTER: Gerard Sheehan

LAB HEAD: Prof Kevin Kavanagh

PROVIDER: PXD011997 | Pride | 2019-01-17

REPOSITORIES: Pride

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Publications

Proteomic Analysis of the Responses of Candida albicans during Infection of Galleria mellonella Larvae.

Sheehan Gerard G Kavanagh Kevin K

Journal of fungi (Basel, Switzerland) 20190111 1

This study assessed the development of disseminated candidiasis within Galleria mellonella larvae and characterized the proteomic responses of Candida albicans to larval hemolymph. Infection of larvae with an inoculum of 1 × 10⁶ yeast cells reduced larval viability 24 (53.33 ± 3.33%), 48 (33.33 ± 3.33%) and 72 (6.66 ± 3.33%) h post infection. C. albicans infection quickly disseminated from the site of inoculation and the presence of yeast and hyphal forms were found in nodul ...[more]

PMID: 30641883

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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 responses of Candida albicans to Galleria mellonella larvae hemolymph

Publications

Proteomic Analysis of the Responses of <i>Candida albicans</i> during Infection of <i>Galleria mellonella</i> Larvae.

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