p Aspergillus fumigatus and aspergillosis: From basics to clinics

Arastehfar A., Carvalho A., Houbraken J., Lombardi L., Garcia-Rubio R., Jenks J. D., ...Daha Fazla

STUDIES IN MYCOLOGY, cilt.100, sa.100, 2021 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 100 Sayı: 100
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1016/j.simyco.2021.100115
  • Dergi Adı: STUDIES IN MYCOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Directory of Open Access Journals
  • Anahtar Kelimeler: Aspergillus fumigatus, Azole-resistance, Drug-resistance mechanism, Invasive aspergillosis, INVASIVE PULMONARY ASPERGILLOSIS, IN-VITRO SUSCEPTIBILITY, BRONCHOALVEOLAR LAVAGE FLUID, ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS, CHRONIC GRANULOMATOUS-DISEASE, DESORPTION IONIZATION-TIME, LIPOSOMAL AMPHOTERICIN-B, FLIGHT MASS-SPECTROMETRY, POSACONAZOLE PLASMA-CONCENTRATIONS, SINGLE NUCLEOTIDE POLYMORPHISMS
  • Çukurova Üniversitesi Adresli: Evet

Özet

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 azoleresistant 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.