title: Galleria mellonella as a host model to study Aspergillus terreus virulence and amphotericin B resistance.
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.
authors.affiliation: a Division of Hygiene and Medical Microbiology; Medical University of Innsbruck ; Innsbruck , Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maurer
authors.affiliation: b Medical Mycology Unit; Department of Biology; Maynooth University ; Maynooth ; Kildare , Ireland.
authors.forename: Niall
authors.initials: N
authors.lastname: Browne
authors.affiliation: b Medical Mycology Unit; Department of Biology; Maynooth University ; Maynooth ; Kildare , Ireland.
authors.forename: Carla
authors.initials: C
authors.lastname: Surlis
authors.affiliation: a Division of Hygiene and Medical Microbiology; Medical University of Innsbruck ; Innsbruck , Austria.
authors.forename: Emina
authors.initials: E
authors.lastname: Jukic
authors.affiliation: c Department of Pathology ; Medical University of Innsbruck ; Innsbruck , Austria.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Moser
authors.affiliation: b Medical Mycology Unit; Department of Biology; Maynooth University ; Maynooth ; Kildare , Ireland.
authors.forename: Kevin
authors.initials: K
authors.lastname: Kavanagh
authors.affiliation: a Division of Hygiene and Medical Microbiology; Medical University of Innsbruck ; Innsbruck , Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.affiliation: a Division of Hygiene and Medical Microbiology; Medical University of Innsbruck ; Innsbruck , Austria.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Binder
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage*; D001230:Aspergillus / Q000187:drug effects* / Q000254:growth & development*; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D006434:Hemocytes / Q000276:immunology; D007814:Larva / Q000254:growth & development / Q000276:immunology / Q000382:microbiology / Q000502:physiology; D007915:Lepidoptera / Q000254:growth & development / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D016019:Survival Analysis; D016896:Treatment Outcome; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B
keywords: Galleria mellonella; amphotericin B resistant and susceptible A. terreus strain cluster; invertebrate in vivo model