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通过靶向萌发治疗曲霉病的新方法

Novel Treatment Approach for Aspergilloses by Targeting Germination.

作者信息

Verburg Kim, van Neer Jacq, Duca Margherita, de Cock Hans

机构信息

Molecular Microbiology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands.

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.

出版信息

J Fungi (Basel). 2022 Jul 22;8(8):758. doi: 10.3390/jof8080758.

Abstract

Germination of conidia is an essential process within the life cycle and plays a major role during the infection of hosts. Conidia are able to avoid detection by the majority of leukocytes when dormant. Germination can cause severe health problems, specifically in immunocompromised people. Aspergillosis is most often caused by () and affects neutropenic patients, as well as people with cystic fibrosis (CF). These patients are often unable to effectively detect and clear the conidia or hyphae and can develop chronic non-invasive and/or invasive infections or allergic inflammatory responses. Current treatments with (tri)azoles can be very effective to combat a variety of fungal infections. However, resistance against current azoles has emerged and has been increasing since 1998. As a consequence, patients infected with resistant have a reported mortality rate of 88% to 100%. Especially with the growing number of patients that harbor azole-resistant Aspergilli, novel antifungals could provide an alternative. Aspergilloses differ in defining characteristics, but germination of conidia is one of the few common denominators. By specifically targeting conidial germination with novel antifungals, early intervention might be possible. In this review, we propose several morphotypes to disrupt conidial germination, as well as potential targets. Hopefully, new antifungals against such targets could contribute to disturbing the ability of Aspergilli to germinate and grow, resulting in a decreased fungal burden on patients.

摘要

分生孢子的萌发是生命周期中的一个重要过程,在宿主感染过程中起主要作用。分生孢子在休眠时能够避免被大多数白细胞检测到。萌发会导致严重的健康问题,特别是在免疫功能低下的人群中。曲霉病最常由()引起,影响中性粒细胞减少的患者以及囊性纤维化(CF)患者。这些患者通常无法有效地检测和清除分生孢子或菌丝,可能会发展为慢性非侵袭性和/或侵袭性感染或过敏性炎症反应。目前使用(三)唑类药物进行治疗对于对抗多种真菌感染可能非常有效。然而,自1998年以来,对当前唑类药物的耐药性已经出现并且一直在增加。因此,感染耐药菌的患者报告的死亡率为88%至100%。特别是随着携带唑类耐药曲霉的患者数量不断增加,新型抗真菌药物可能会提供一种替代方案。曲霉病在定义特征上有所不同,但分生孢子的萌发是少数几个共同特征之一。通过用新型抗真菌药物特异性地靶向分生孢子的萌发,可能实现早期干预。在这篇综述中,我们提出了几种破坏分生孢子萌发的形态类型以及潜在靶点。希望针对这些靶点的新型抗真菌药物能够有助于干扰曲霉萌发和生长的能力,从而减轻患者的真菌负荷。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7844/9331470/998e1e0e398f/jof-08-00758-g001.jpg

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