Aspergillus fumigatus and aspergillosis: From basics to clinics

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 emerge...

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Detalles Bibliográficos
Autores: Arastehfar, Amir, Carvalho, Agostinho, Houbraken, Jos A.M.P., Lombardi, Lisa, Gabaldón, Toni
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Politècnica de Catalunya (UPC)
Repositorio:UPCommons. Portal del coneixement obert de la UPC
Idioma:inglés
OAI Identifier:oai:upcommons.upc.edu:2117/345996
Acceso en línea:https://hdl.handle.net/2117/345996
https://dx.doi.org/10.1016/j.simyco.2021.100115
Access Level:acceso abierto
Palabra clave:Aspergillus fumigatus
Azoles
Biotechnology
Azole-resistance
Drug-resistance mechanism
Invasive aspergillosis
Infecció
Àrees temàtiques de la UPC::Informàtica::Aplicacions de la informàtica::Bioinformàtica
Descripción
Sumario: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.