Περίληψη:
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.
Συγγραφείς:
Arastehfar, A.
Carvalho, A.
Houbraken, J.
Lombardi, L. and
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.
Gabaldon, T. and
Meletiadis, J.
Kostrzewa, M.
Pan, W.
Lass-Floerl, C. and
Perlin, D. S.
Hoenigl, M.
