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在小鼠模型中比较耳念珠菌、近平滑念珠菌、光滑念珠菌和白色念珠菌的毒力。

Comparative virulence of Candida auris with Candida haemulonii, Candida glabrata and Candida albicans in a murine model.

机构信息

Department of Medical Parasitology and Mycology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

Mycoses. 2018 Jun;61(6):377-382. doi: 10.1111/myc.12754. Epub 2018 Mar 14.

DOI:10.1111/myc.12754
PMID:29460345
Abstract

The incidence of invasive fungal infections (IFIs) caused by uncommon Candida species with diverse virulence and susceptibility profiles has increased in recent years. Due to scarce clinical and experimental data on the pathogenicity of Candida auris, the aim of this study was to evaluate and compare the virulence of two rare clinically relevant species, C. auris and Candida haemulonii with Candida glabrata and Candida albicans in an immunocompetent murine model of disseminated infection. Immunocompetent ICR female mice were infected with three inoculum sizes (1 × 10 , 1 × 10 and 1 × 10 CFU/mouse) of two C. auris strains and one isolate of C. haemulonii, C. glabrata and C. albicans. Tissue burden on days 5 and 10 postchallenge and mortality rate were used as virulence markers. A high virulence was found for C. albicans, followed by C. auris, C. glabrata and C. haemulonii, respectively. Candida albicans showed high virulence with a medium survival time of 9.5 days for mice infected with 1 × 10 CFU/mouse. For inocula at 1 × 10 and 1 × 10 CFU/mouse, there were significant differences in fungal burden at day 10 between C. albicans, C. auris and C. glabrata isolates compared with C. haemulonii (P < .0001). Overall, no significant differences between C. albicans with C. auris and C. glabrata were observed in mice infected with three different inocula (P > .05). In general, the highest fungal load of all isolates was detected in kidney followed by spleen, liver and lung tested with three different inocula on the two different experimental days. Histopathological examination revealed the abundant presence of yeast cells with pseudohyphae for C. albicans and only yeast cells for C. auris, C. glabrata and C. haemulonii, in all the kidney tissue samples. In conclusion, C. albicans is a highly virulent opportunistic fungus, as the clinical and experimental data demonstrate, and also our results demonstrate a low virulence of C. haemulonii in immunocompetent animals. Altogether, this study highlights the pathogenic potential of C. auris.

摘要

近年来,由毒力和药敏谱各异的罕见念珠菌引起的侵袭性真菌感染(IFI)发病率有所增加。由于关于耳念珠菌致病性的临床和实验数据稀缺,本研究旨在评估和比较两种罕见的临床相关种属——耳念珠菌和粘红酵母,以及光滑念珠菌和白色念珠菌在免疫功能正常的播散性感染小鼠模型中的毒力。用三种接种量(1×10 、1×10 和 1×10 CFU/只)的两种耳念珠菌株和一株粘红酵母、光滑念珠菌和白色念珠菌感染免疫功能正常的 ICR 雌性小鼠。用组织负荷和死亡率作为毒力标志物,分别在感染后第 5 天和第 10 天进行检测。结果发现,白色念珠菌的毒力最高,其次是耳念珠菌、光滑念珠菌和粘红酵母。白色念珠菌的毒力最高,感染 1×10 CFU/只的小鼠中位存活时间为 9.5 天。对于 1×10 和 1×10 CFU/只的接种量,与粘红酵母相比,感染白色念珠菌、耳念珠菌和光滑念珠菌的小鼠在第 10 天的真菌负荷有显著差异(P<0.0001)。总的来说,在感染三种不同接种量的小鼠中,白色念珠菌与耳念珠菌和光滑念珠菌之间没有观察到显著差异(P>.05)。一般来说,在两个不同的实验日,用三种不同的接种量,在肾脏中检测到所有分离株的真菌负荷最高,其次是脾脏、肝脏和肺。组织病理学检查显示,在所有肾脏组织样本中,白色念珠菌存在大量酵母细胞和假菌丝,而耳念珠菌、光滑念珠菌和粘红酵母仅存在酵母细胞。总之,正如临床和实验数据所表明的,白色念珠菌是一种高度毒力的机会性真菌,我们的结果也表明粘红酵母在免疫功能正常的动物中具有低毒力。总的来说,这项研究强调了耳念珠菌的致病性。

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