Galleria mellonella as a model system to study virulence potential of mucormycetes and evaluation of antifungal treatment.

Galleria mellonella as a model system to study virulence potential of mucormycetes and evaluation of antifungal treatment.
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Mellonella Galleria作为研究粘液菌的毒力潜力和抗真菌治疗评估的模型系统。

DOI:
10.1093/mmy/myy042
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发表时间:
2019-04-01
期刊:
影响因子:
2.9
通讯作者:
Binder U
Binder U
中科院分区:
医学3区
文献类型:
--
作者:
Maurer E;Hörtnagl C;Lackner M;Grässle D;Naschberger V;Moser P;Segal E;Semis M;Lass-Flörl C;Binder U

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毛霉菌可引起皮肤至深部感染,主要发生在免疫功能低下的宿主中,由于治疗延迟和无效,导致高死亡率。在这项研究中,将大蜡螟幼虫作为异源无脊椎动物宿主进行评估,以研究临床相关的毛霉(根霉属,根毛霉属,Lichtheimia spp.,毛霉属(Mucor spp.)所有供试种均能感染G.大蜡螟幼虫毒力潜力是物种特异性的,并与临床相关性。受感染幼虫的存活率取决于(a)种属(生长速度和孢子大小),(B)感染剂量,(c)孵育温度,(d)氧化应激耐受性和(e)生长培养基中的铁可用性。此外,我们还利用了G。Mellonella系统来测定脂质体阿替霉素B、泊沙康唑、艾沙康唑和制霉菌素-吲哚美辛的抗真菌功效。体内治疗的结果在很大程度上取决于所用药物和供试种属。制霉菌素-吲哚美辛对毛霉目表现出最好的活性,其次是泊沙康唑,而脂质体阿替霉素B和艾沙康唑的疗效有限。在这种替代宿主系统中测试的抗真菌药的药代动力学特性部分解释了有限的治疗效果。最后,G. Mellonella代表了一个有用的无脊椎动物感染模型,用于研究毛霉菌的毒力,而治疗反应的评估是有限的。
Mucorales can cause cutaneous to deep-seated infections, mainly in the immunocompromised host, resulting in high mortality rates due to late and inefficient treatment. In this study, Galleria mellonella larvae were evaluated as a heterologous invertebrate host to study pathogenicity of clinically relevant mucormycetes (Rhizopus spp., Rhizomucor spp., Lichtheimia spp., Mucor spp.). All tested species were able to infect G. mellonella larvae. Virulence potential was species-specific and correlated to clinical relevance. Survival of infected larvae was dependent on (a) the species (growth speed and spore size), (b) the infection dose, (c) the incubation temperature, (d) oxidative stress tolerance, and (e) iron availability in the growth medium. Moreover, we exploited the G. mellonella system to determine antifungal efficacy of liposomal amphotericin B, posaconazole, isavuconazole, and nystatin-intralipid. Outcome of in vivo treatment was strongly dependent upon the drug applied and the species tested. Nystatin-intralipid exhibited best activity against Mucorales, followed by posaconazole, while limited efficacy was seen for liposomal amphotericin B and isavuconazole. Pharmacokinetic properties of the tested antifungals within this alternative host system partly explain the limited treatment efficacy. In conclusion, G. mellonella represents a useful invertebrate infection model for studying virulence of mucormycetes, while evaluation of treatment response was limited.
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发表时间: 2013-07-01
期刊: MEDICAL MYCOLOGY
影响因子: 2.9
作者:
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烟曲霉的分生物色突变体对异源昆虫宿主Galleria mellonella具有高度致病性。
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发表时间: 2009
期刊: PloS one
影响因子: 3.7
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