Maurer Elisabeth, Browne Niall, Surlis Carla, Jukic Emina, Moser Patrizia, Kavanagh Kevin, Lass-Flörl Cornelia, Binder Ulrike
a Division of Hygiene and Medical Microbiology; Medical University of Innsbruck ; Innsbruck , Austria.
b Medical Mycology Unit; Department of Biology; Maynooth University ; Maynooth ; Kildare , Ireland.
Virulence. 2015;6(6):591-8. doi: 10.1080/21505594.2015.1045183. Epub 2015 Jun 24.
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.
（i）确定两性霉素B（AMB）耐药和敏感的土曲霉分离株在致病性上的差异；（ii）评估AMB在体内的疗效；（iii）并将结果与体外药敏数据相关联。用2株对AMB耐药的土曲霉（ATR）和3株对AMB敏感的土曲霉（ATS）分离株感染幼虫，并将存活率与幼虫血细胞的生理特性和杀伤能力相关联。此外，用不同浓度的脂质体两性霉素B（L-AMB）处理感染的幼虫。测定血细胞密度以评估L-AMB对幼虫免疫细胞的影响。幼虫对土曲霉感染的敏感性呈接种量和温度依赖性。对L-AMB的体外药敏与抗真菌治疗的体内结果相关，确定了土曲霉的一个AMB敏感菌株簇。在幼虫模型中，对L-AMB的敏感性增加了毒力潜能，但这种增加也与更快的生长以及幼虫血细胞造成的损伤较小相一致。L-AMB处理通过增加血细胞密度启动了幼虫免疫反应。黄粉虫为体内筛选土曲霉毒力和治疗方案提供了一个便捷的模型，有助于提出一个可在哺乳动物模型的精细实验中进一步检验的假设。
