PDF(Pubmed)
Abstract：
Mucorales species cause debilitating, life-threatening sinopulmonary diseases in immunocompromised patients and penetrating wounds in trauma victims. Common antifungal agents against mucormycosis have significant toxicity and are often ineffective. To evaluate treatments against mucormycosis, sporangiospores are typically used for in vitro assays and in pre-clinical animal models of pulmonary infections. However, in clinical cases of wound mucormycosis caused by traumatic inoculation, hyphal elements found in soil are likely the form of the inoculated organism. In this study, Galleria mellonella larvae were infected with either sporangiospores or hyphae of Rhizopus arrhizus and Lichtheimia corymbifera. Hyphal infections resulted in greater and more rapid larval lethality than sporangiospores, with an approximate 10-16-fold decrease in LD50 of hyphae for R. arrhizus (p = 0.03) and L. corymbifera (p = 0.001). Liposomal amphotericin B, 10 mg/kg, was ineffective against hyphal infection, while the same dosage was effective against infections produced by sporangiospores. Furthermore, in vitro, antifungal susceptibility studies show that minimum inhibitory concentrations of several antifungal agents against hyphae were higher when compared to those of sporangiospores. These findings support using hyphal elements of Mucorales species for virulence testing and antifungal drug screening in vitro and in G. mellonella for studies of wound mucormycosis.
摘要：
毛虫物种会导致衰弱，免疫功能低下患者的危及生命的鼻肺疾病和创伤受害者的穿透性伤口。针对毛霉菌病的常见抗真菌剂具有显著的毒性并且通常是无效的。为了评估毛霉菌病的治疗方法，孢子囊孢子通常用于体外测定和肺部感染的临床前动物模型。然而,在创伤接种引起的伤口毛霉菌病的临床病例中，在土壤中发现的菌丝元素可能是接种生物的形式。在这项研究中,海绵状芽孢杆菌幼虫感染了孢子孢子或根霉和曲霉菌的菌丝。菌丝感染导致的幼虫致死率比孢子孢子更大，更快，与约10-16倍的LD50的菌丝的下降。arrhizus（p=0.03）和L.Corymbifera（p=0.001）。脂质体两性霉素B,10mg/kg,对菌丝感染无效，而相同的剂量对孢子孢子产生的感染有效。此外，在体外，抗真菌药物敏感性研究表明，与孢子囊孢子相比，几种抗真菌药物对菌丝的最低抑制浓度更高。这些发现支持使用Mucorales物种的菌丝元素进行体外毒力测试和抗真菌药物筛选，并在G.mellonella中用于伤口毛霉菌病的研究。
