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氟康唑耐药耳念珠菌V型在小鼠模型中的致病性评估

Pathogenicity Evaluation on Fluconazole-Resistant Candida auris Clade V in Murine Model.

作者信息

Barough Robab Ebrahimi, Badali Hamid, Amiri Fereshteh Talebpour, Javidnia Javad, Shahrokh Somayeh, Siahposht-Khachaki Ali, Moazeni Maryam, Sarvi Shahabeddin, Valadan Reza, Moosazadeh Mahmood, Nosratabadi Mohsen, Basirpour Bahare, Faeli Leila, Haghani Iman, Meis Jacques F, Abastabar Mahdi

机构信息

Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Mycopathologia. 2025 Jun 24;190(4):58. doi: 10.1007/s11046-025-00963-5.

DOI:10.1007/s11046-025-00963-5
PMID:40555808
Abstract

BACKGROUND

Candida auris, a medically multidrug-resistant fungal pathogen, has recently emerged as the primary one that poses a global public health threat. Although C. auris was first described in Japan, numerous cases of C. auris infections have been reported globally and clustered in four major clades (I, II, III, and IV). In 2019 and 2024, a potential V clade in Iran and VI clade in Bangladesh were described. Nevertheless, limited pathogenicity data of the fifth clade are available compared to the other clades.

OBJECTIVES AND METHODS

This study evaluated the pathogenicity of fluconazole-resistant C. auris clade V and the therapeutic efficacy of amphotericin B in an immunocompromised mouse model, with C. albicans serving as a standard pathogen. The infection's advancement was tracked by evaluating mortality rates, fungal burden, and histopathological alterations.

RESULTS

The C. auris clade V strain exhibited the highest fungal load in heart and kidney tissues on days 3, 5, 7, and 10, with the lowest load observed in brain tissue. In contrast, mice infected with the C. albicans strain showed the highest fungal load in the spleen on days 3, 5, and 10 and in the heart on the 7th day post-infection. Conversely, the average survival time for mice infected with C. auris was 14 days with drug treatment, demonstrating that AMB treatment significantly improved the survival rate of mice infected with C. auris clade V.

CONCLUSION

This study highlights the differing pathogenic behaviors of C. auris clade V and C. albicans. Although C. albicans exhibits greater virulence in untreated infections, C. auris clade V remains a serious threat, even at lower colony levels. The improved survival rates in infected mice treated with amphotericin B underscore the importance of effective therapeutic interventions. Further research is essential to enhance our understanding of these pathogens and optimize treatment protocols.

摘要

背景

耳念珠菌是一种具有多重耐药性的医学真菌病原体,最近已成为对全球公共卫生构成威胁的主要病原体。尽管耳念珠菌最早在日本被描述,但全球已报告了大量耳念珠菌感染病例,并聚集在四个主要分支(I、II、III和IV)中。2019年和2024年,分别在伊朗描述了一个潜在的V分支,在孟加拉国描述了VI分支。然而,与其他分支相比,关于第五分支的致病性数据有限。

目的和方法

本研究在免疫受损小鼠模型中评估了耐氟康唑的耳念珠菌V分支的致病性以及两性霉素B的治疗效果,以白色念珠菌作为标准病原体。通过评估死亡率、真菌负荷和组织病理学改变来追踪感染的进展。

结果

在感染后第3、5、7和10天,耳念珠菌V分支菌株在心脏和肾脏组织中的真菌负荷最高,在脑组织中观察到的负荷最低。相比之下,感染白色念珠菌菌株的小鼠在感染后第3、5和10天脾脏中的真菌负荷最高,在第7天心脏中的真菌负荷最高。相反,接受药物治疗的感染耳念珠菌小鼠的平均存活时间为14天,这表明两性霉素B治疗显著提高了感染耳念珠菌V分支小鼠的存活率。

结论

本研究突出了耳念珠菌V分支和白色念珠菌不同的致病行为。尽管白色念珠菌在未经治疗的感染中表现出更强的毒力,但耳念珠菌V分支即使在较低的菌落水平下仍然是一个严重威胁。用两性霉素B治疗感染小鼠后存活率的提高强调了有效治疗干预措施的重要性。进一步的研究对于加深我们对这些病原体的理解和优化治疗方案至关重要。

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本文引用的文献

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Genotypic and phenotypic characterisation of a nosocomial outbreak of Candida auris in Spain during 5 years.西班牙5年间耳念珠菌医院感染暴发的基因型和表型特征
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Multicenter Candida auris outbreak caused by azole-susceptible clade IV in Pernambuco, Brazil.巴西伯南布哥州由唑类药物敏感性 IV 分支引起的多中心耳念珠菌暴发。
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Nosocomial infection of C. auris in COVID-19 Intensive Care Unit in Türkiye and Phylogenetic Analysis of Isolates.土耳其新冠肺炎重症监护病房中耳念珠菌的医院感染及分离株的系统发育分析
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Study of Candidemia and its Antifungal Susceptibility Profile at the University Hospital of Montevideo, Uruguay.乌拉圭蒙得维的亚大学医院的念珠菌血症及其抗真菌药敏谱研究。
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Utility of CHROMagar™ Candida Plus for presumptive identification of Candida auris from surveillance samples.CHROMagar™ Candida Plus 对监测样本中疑似耳念珠菌的鉴定效用。
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Drug repurposing against Candida auris: A systematic review.抗耳念珠菌药物再利用:系统评价。
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In Vivo Efficacy of Amphotericin B against Four Clades.两性霉素B对四个进化枝的体内疗效
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