Exploring the intersection of Aspergillus fumigatus biofilms, infections, immune response and antifungal resistance

Aspergillus fumigatus is an opportunistic pathogen that primarily affects the lungs and frequently elicits an allergic immune response in human hosts via inhalation of its airborne asexual spores (conidia). In immunocompromised individuals, the conidia of this fungus can germinate in the lung and result in severe systemic infections characterised by widespread tissue and organ damage. Conversely, in healthy hosts, the innate immune system is instrumental in eliminating the conidia and preventing disease progression. As with numerous other pathogenic fungi, A. fumigatus possesses a set of virulence factors that facilitate its infective mechanism and the circumvention of immune defences in susceptible hosts. The intrinsic capacity of A. fumigatus to form complex 3D-structured biofilms, both on biotic and abiotic surfaces, represents a key determinant of its evasion of the host immune system and resistance to antifungal drugs. This review delineates the pivotal role of A. fumigatus biofilm structure and function as a significant virulence factor in pathogenic infections, such as aspergilloma and invasive pulmonary aspergillosis (IPA). Additionally, we discuss the importance for the development of novel antifungal drugs as drug-resistant strains continue to evolve. Furthermore, co-infections of A. fumigatus with other nosocomial pathogens have a substantial impact on patient's health outcomes. In this context, we provide a brief overview of COVID-19-associated pulmonary aspergillosis (CAPA), a recently documented condition that has gained attention due to its associated high degree of severity.