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在“组学”时代理解毛霉病

Understanding Mucormycoses in the Age of "omics".

作者信息

Soare Alexandra Y, Watkins Tonya N, Bruno Vincent M

机构信息

Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, United States.

Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States.

出版信息

Front Genet. 2020 Jun 30;11:699. doi: 10.3389/fgene.2020.00699. eCollection 2020.

Abstract

Mucormycoses are deadly invasive infections caused by several fungal species belonging to the subphylum Mucoromycotina, order . Hallmarks of disease progression include angioinvasion and tissue necrosis that aid in fungal dissemination through the blood stream, causing deeper infections and resulting in poor penetration of antifungal agents to the site of infection. In the absence of surgical removal of the infected focus, antifungal therapy alone is rarely curative. Even when surgical debridement is combined with high-dose antifungal therapy, the mortality associated with mucormycoses is >50%. The unacceptably high mortality rate, limited options for therapy and the extreme morbidity of highly disfiguring surgical therapy provide a clear mandate to understand the molecular mechanisms that govern pathogenesis with the hopes of developing alternative strategies to treat and prevent mucormycoses. In the absence of robust forward and reverse genetic systems available for this taxonomic group of fungi, unbiased next generation sequence (NGS)-based approaches have provided much needed insights into our understanding of many aspects of Mucormycoses, including genome structure, drug resistance, diagnostic development, and fungus-host interactions. Here, we will discuss the specific contributions that NGS-based approaches have made to the field and discuss open questions that can be addressed using similar approaches.

摘要

毛霉病是由毛霉亚门的几种真菌引起的致命性侵袭性感染。疾病进展的标志包括血管侵袭和组织坏死,这有助于真菌通过血流传播,导致更深层次的感染,并导致抗真菌药物难以渗透到感染部位。在没有手术切除感染灶的情况下,仅使用抗真菌治疗很少能治愈。即使手术清创与高剂量抗真菌治疗相结合,毛霉病相关的死亡率仍>50%。高得令人无法接受的死亡率、有限的治疗选择以及高度毁容性手术治疗带来的极高发病率,明确要求我们了解控制发病机制的分子机制,以期开发出治疗和预防毛霉病的替代策略。由于缺乏适用于这一真菌分类群的强大正向和反向遗传系统,基于新一代测序(NGS)的无偏倚方法为我们理解毛霉病的许多方面提供了急需的见解,包括基因组结构、耐药性、诊断开发以及真菌与宿主的相互作用。在此,我们将讨论基于NGS的方法对该领域所做出的具体贡献,并讨论可以使用类似方法解决的开放性问题。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4464/7339291/d0cfa228e4f8/fgene-11-00699-g001.jpg

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