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Aspergillus fumigatus and aspergillosis: From basics to clinics
Studies in Mycology ( IF 14.1 ) Pub Date : 2021-05-10 , DOI: 10.1016/j.simyco.2021.100115
A Arastehfar 1 , A Carvalho 2, 3 , J Houbraken 4 , L Lombardi 5 , R Garcia-Rubio 1 , J D Jenks 6, 7 , O Rivero-Menendez 8 , R Aljohani 9 , I D Jacobsen 10, 11 , J Berman 12 , N Osherov 13 , M T Hedayati 14 , M Ilkit 15 , D Armstrong-James 9 , T Gabaldón 16, 17, 18, 19 , J Meletiadis 20 , M Kostrzewa 21 , W Pan 22 , C Lass-Flörl 23 , D S Perlin 1 , M Hoenigl 6, 24, 25
Affiliation  

The airborne fungus Aspergillus fumigatus poses a serious health threat to humans by causing numerous invasive infections and a notable mortality in humans, especially in immunocompromised patients. Mould-active azoles are the frontline therapeutics employed to treat aspergillosis. The global emergence of azole-resistant A. fumigatus isolates in clinic and environment, however, notoriously limits the therapeutic options of mould-active antifungals and potentially can be attributed to a mortality rate reaching up to 100 %. Although specific mutations in CYP51A are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type CYP51A genotype challenging the efficacy of the current diagnostic tools. Therefore, applications of whole-genome sequencing are increasingly gaining popularity to overcome such challenges. Prominent echinocandin tolerance, as well as liver and kidney toxicity posed by amphotericin B, necessitate a continuous quest for novel antifungal drugs to combat emerging azole-resistant A. fumigatus isolates. Animal models and the tools used for genetic engineering require further refinement to facilitate a better understanding about the resistance mechanisms, virulence, and immune reactions orchestrated against A. fumigatus. This review paper comprehensively discusses the current clinical challenges caused by A. fumigatus and provides insights on how to address them.



中文翻译:

烟曲霉和曲霉病:从基础知识到临床

空气中的真菌烟曲霉对人类造成严重的健康威胁,它会引起大量的侵袭性感染,并导致人类(尤其是免疫功能低下的患者)显着死亡。霉菌活性唑类药物是治疗曲霉病的一线疗法。全球出现抗唑类A然而,众所周知,临床和环境中的烟曲霉分离株限制了霉菌活性抗真菌药物的治疗选择,并且可能导致高达 100% 的死亡率。尽管CYP 51A的特异性突变是唑类耐药的主要原因,但具有野生型CYP 51A基因型的新一波唑类耐药分离株对当前诊断工具的功效提出了挑战。因此,全基因组测序的应用越来越受欢迎,以克服这些挑战。突出的棘白菌素耐受性以及两性霉素 B 引起的肝脏和肾脏毒性,需要不断寻求新型抗真菌药物来对抗新出现的唑类抗药性A。烟熏分离物。用于基因工程的动物模型和工具需要进一步完善,以促进更好地了解针对A 的耐药机制、毒力和免疫反应。烟草这篇综述文章全面讨论了当前由A引起的临床挑战。fumigatus并提供了有关如何解决这些问题的见解。

更新日期:2021-05-10
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