The non-mammalian host Galleria mellonella can be used to study the virulence of the fungal pathogen Candida tropicalis and the efficacy of antifungal drugs during infection by this pathogenic yeast
The non-mammalian host Galleria mellonella can be used to study the virulence of the fungal pathogen Candida tropicalis and the efficacy of antifungal drugs during infection by this pathogenic yeast
复制标题
DOI：
10.3109/13693786.2012.737031
复制
发表时间：
2013-07-01
期刊：
影响因子：
2.9
通讯作者：
Zaragoza, Oscar
中科院分区：
文献类型：
--
作者：
Cecilia Mesa-Arango, Ana;Forastiero, Agustina;Zaragoza, Oscar
虽然热带假丝酵母是侵袭性真菌疾病的常见原因，但其与宿主的相互作用仍缺乏研究。Galleria mellonella是鳞翅目昆虫的一种模式生物，为研究不同微生物的毒力和药物的药效提供了一个有用的工具。本工作研究了C. tropicalis在G.不同温度下的大蜡螟以及抗真菌药物在该感染模型中的疗效。当用不同浓度的酵母接种物悬浮液（4 × 10（6）、2 × 10（6）、10（6）和5 × 10（5）个细胞/幼虫）感染幼虫时，我们观察到对杀死昆虫的剂量依赖性效应（50%存活率范围为1.4 +/- 0.8至8.8 +/- 1.2天，分别使用较高和较低的接种物）。热带假丝酵母对G.在30 ° C和37 ° C下，Mellonella幼虫的毒力更明显，但在37 ° C下。血细胞吞噬C.感染2小时后，Tropicalis细胞的吞噬率，虽然与其他真菌病原体如新生隐球菌相比，吞噬率较低。在感染过程中，血淋巴中血细胞密度降低，酵母菌在G.梅隆内拉在不同浓度下测试了阿替霉素B、卡泊芬净、氟康唑和伏立康唑的效力，并且在等效于治疗剂量的浓度下观察到所有药物的保护作用。在感染期间，感染幼虫中的真菌负荷增加，并且阿替霉素B和氟康唑减少了蠕虫中的菌落形成单位的数量。此外，抗真菌治疗与感染区域周围细胞聚集体的存在有关。我们的结论是G. mellonella为研究C.热带假单胞菌的毒力和药效。
Although Candida tropicalis is a frequent cause of invasive fungal diseases, its interaction with the host remains poorly studied. Galleria mellonella is a Lepidoptera model which offers a useful tool to study virulence of different microorganisms and drug efficacy. In this work we investigated the virulence of C. tropicalis in G. mellonella at different temperatures and the efficacy of antifungal drugs in this infection model. When larvae were infected with yeast inocula suspensions of different concentrations (4 x 10(6), 2 x 10(6), 10(6) and 5 x 10(5) cells/larva), we observed a dose-dependent effect on the killing of the insect (50% survival ranging from 1.4 +/- 0.8 to 8.8 +/- 1.2 days with the higher and lower inocula, respectively). Candida tropicalis killed G. mellonella larvae at both 30 degrees C and 37 degrees C, although at 37 degrees C the virulence was more evident. Haemocytes phagocytosed C. tropicalis cells after 2 hours of infection, although the phagocytosis rate was lower when compared with other fungal pathogens, such as Cryptococcus neoformans. Moreover, the haemocyte density in the haemolymph decreased during infection and the yeast formed pseudohyphae in G. mellonella. The efficacy of amphotericin B, caspofungin, fluconazole and voriconazole was tested at different concentrations, and a protective effect was observed with all the drugs at concentrations equivalent to therapeutic dose. Fungal burden increased in infected larvae during time of infection and amphotericin B and fluconazole reduced the number of colony-forming units in the worms. Moreover, antifungal treatment was associated with the presence of cell aggregates around infected areas. We conclude that G. mellonella offers a simple and feasible model to study C. tropicalis virulence and drug efficacy.