Galleria mellonella as a host model to study Aspergillus terreus virulence and amphotericin B resistance

Virulence. 2015;6(6):591-8. doi: 10.1080/21505594.2015.1045183. Epub 2015 Jun 24.

Abstract

The aim of this study was to investigate if the alternative in vivo model Galleria mellonella can be used (i) to determine differences in pathogenicity of amphotericin B (AMB) resistant and susceptible A. terreus isolates, (ii) to evaluate AMB efficacy in vivo (iii) and to correlate outcome to in vitro susceptibility data. Larvae were infected with 2 A. terreus AMB resistant (ATR) and 3 AMB susceptible (ATS) isolates and survival rates were correlated to physiological attributes and killing ability of larval haemocytes. Additionally, infected larvae were treated with different concentrations of L-AMB. Haemocyte density were ascertained to evaluate the influence of L-AMB on the larval immune cells. Larvae were sensitive to A. terreus infection in an inoculum-size and temperature dependent manner. In vitro susceptibility to L-AMB correlated with in vivo outcome of antifungal treatment, defining an AMB susceptible strain cluster of A. terreus. Susceptibility to L-AMB increased virulence potential in the larval model, but this increase was also in accordance with faster growth and less damage caused by larval haemocytes. L-AMB treatment primed the larval immune response by increasing haemocyte density. G. mellonella provides a convenient model for the in vivo screening of A. terreus virulence and treatment options, contributing to the generation of a hypothesis that can be further tested in refined experiments in mammalian models.

Keywords: Galleria mellonella; amphotericin B resistant and susceptible A. terreus strain cluster; invertebrate in vivo model.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphotericin B / administration & dosage*
  • Animals
  • Antifungal Agents / administration & dosage*
  • Aspergillus / drug effects*
  • Aspergillus / growth & development*
  • Disease Models, Animal
  • Drug Resistance, Fungal*
  • Hemocytes / immunology
  • Larva / growth & development
  • Larva / immunology
  • Larva / microbiology
  • Larva / physiology
  • Lepidoptera / growth & development
  • Lepidoptera / immunology
  • Lepidoptera / microbiology*
  • Lepidoptera / physiology
  • Survival Analysis
  • Treatment Outcome
  • Virulence

Substances

  • Antifungal Agents
  • Amphotericin B