Understanding the fundamental role of virulence determinants to combat Aspergillus fumigatus infections: exploring beyond cell wall

Aspergillus fumigatus is a ubiquitous fungal pathogen associated with several life-threatening infections in patients suffering from chronic lung inflammatory diseases and immune deficiencies. Multiple factors contribute towards the survival and adaptation of A. fumigatus in the host and determine its pathogenicity. A limited spectrum of antifungal drugs is available for treating A. fumigatus infections which mainly target either cell wall or cell membrane biosynthesis. The clinical usage of these drugs is becoming progressively restricted due of the emergence of resistant A. fumigatus strains. Thus, there is an urgent unmet need to analyse other virulence determinants of A. fumigatus, in addition to screening suitable and effective targets for the prospective antifungal drugs. The present review elaborates A. fumigatus virulence determinants associated with cell surface organisation such as hydrophobins (rodlet layer formation), chitin, glucans and galactosaminogalactan. Besides, secondary metabolites such as gliotoxin, melanin and siderophores (iron homeostasis mechanism) have also been discussed. The exhaustive understanding of these virulence determinants could potentially lead to the discovery of novel targets that could be exploited to either discover new molecules or enhance the efficacy of known antifungal drugs.