Resistance mechanism and proteins in Aspergillus species against antifungal agents

Aspergillus species contain pathogenic and opportunistic fungal pathogens which have the potential to cause mycosis (invasive aspergillosis) in humans. The existing antifungal drugs have limitation largely due to the development of drug-resistant isolates. To gain insight into the mechanism of action and antifungal drug resistance in Aspergillus species including biofilm formation, we have reviewed protein data of Aspergillus species during interaction with antifungals drugs (polynes, azoles and echinocandin) and phytochemicals (artemisinin, coumarin and quercetin). Our analyses provided a list of Aspergillus proteins (72 proteins) that were abundant during interaction with different antifungal agents. On the other hand, there are 26 proteins, expression level of which is affected by more than two antifungal agents, suggesting the more general response to the stress induced by the antifungal agents. Our analysis showed enzymes from cell wall remodelling, oxidative stress response and energy metabolism are the responsible factors for providing resistance against antifungal drugs in Aspergillus species and could be explored further in clinical isolates. Also, these findings have clinical importance since the effect of drug targeting different proteins can be potentiated by combination therapy. We have also discussed the opportunities ahead to study the functional role of proteins from environmental and clinical isolates of Aspergillus during its interaction with the antifungal drugs.

Abbreviations: IPA: invasive pulmonary aspergillosis; IA: invasive aspergillosis; AmB: Amphotericin B; CAS: Caspofungin; VRC: Voriconazole; ITC: Itraconazole; POS: Posaconazole; ART: Artemisinin; QRT: Quercetin; CMR: Coumarin; MIC: minimal inhibitory concentration