Arastehfar A, Carvalho A, Houbraken J, Lombardi L, Garcia-Rubio R, Jenks J D, Rivero-Menendez O, Aljohani R, Jacobsen I D, Berman J, Osherov N, Hedayati M T, Ilkit M, Armstrong-James D, Gabaldón T, Meletiadis J, Kostrzewa M, Pan W, Lass-Flörl C, Perlin D S, Hoenigl M
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, 07110, USA.
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
Stud Mycol. 2021 May 10;100:100115. doi: 10.1016/j.simyco.2021.100115. eCollection 2021 Sep.
The airborne fungus 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 . 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 are the main cause of azole resistance, there is a new wave of azole-resistant isolates with wild-type 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 . 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 . . This review paper comprehensively discusses the current clinical challenges caused by . and provides insights on how to address them.
这种空气传播的真菌通过引发多种侵袭性感染以及导致人类尤其是免疫功能低下患者的显著死亡率，对人类健康构成严重威胁。含霉菌活性的唑类药物是用于治疗曲霉病的一线治疗药物。然而，临床上和环境中唑类耐药菌株在全球范围内的出现，严重限制了含霉菌活性抗真菌药物的治疗选择，并且可能导致死亡率高达100%。尽管特定基因突变是唑类耐药的主要原因，但出现了一波具有野生型基因型的唑类耐药菌株，对当前诊断工具的有效性构成挑战。因此，全基因组测序的应用越来越受欢迎，以克服此类挑战。棘白菌素耐受性突出，以及两性霉素B造成的肝肾毒性，使得持续寻求新型抗真菌药物来对抗新出现的唑类耐药菌株成为必要。动物模型和用于基因工程的工具需要进一步完善，以促进对耐药机制、毒力以及针对该真菌的免疫反应的更好理解。这篇综述文章全面讨论了由该真菌引起的当前临床挑战，并就如何应对这些挑战提供了见解。
