Gomez-Lopez A, Forastiero A, Cendejas-Bueno E, Gregson L, Mellado E, Howard S J, Livermore J L, Hope W W, Cuenca-Estrella M
Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.
Med Mycol. 2014 Apr;52(3):311-9. doi: 10.1093/mmy/myt022. Epub 2014 Feb 4.
The impact of different mutations in the Aspergillus fumigatus ergosterol biosynthesis pathway on pathogenesis has been evaluated using a simple invertebrate mini host, the caterpillar Galleria mellonella. A set of strains that includes clinical isolates and isogenic mutants with mutations at the cyp51A gene conferring azole resistance were studied. All strains demonstrated a similar in vitro growth pattern and are equally virulent against the insect larvae. These results suggest that in A. fumigatus acquisition of this particular azole-resistance mechanism would not imply any significant change in virulence. G. mellonella may provide a convenient and inexpensive model for the in vivo prescreening of mutants of A. fumigatus, contributing to the generation of a hypotheses that can be further tested in refined experiments in mammalian models.
利用一种简单的无脊椎动物微型宿主——大蜡螟幼虫,评估了烟曲霉麦角固醇生物合成途径中不同突变对致病性的影响。研究了一组菌株,包括临床分离株和在cyp51A基因发生突变而具有唑抗性的同基因突变体。所有菌株在体外均表现出相似的生长模式,并且对昆虫幼虫的毒力相同。这些结果表明,在烟曲霉中获得这种特定的唑抗性机制并不意味着毒力会有任何显著变化。大蜡螟幼虫可为烟曲霉突变体的体内预筛选提供一种方便且廉价的模型,有助于提出可在哺乳动物模型的精细实验中进一步检验的假设。