Virulence determinants and stress resistance of Aspergillus oerlinghausenensis, a close relative of the human pathogen Aspergillus fumigatus

Sammanfattning

Aspergillus fumigatus is the primary cause of invasive aspergillosis, a life-threatening infection with rising incidence, particularly among immunocompromised individuals. Recently, the cryptic species Aspergillus oerlinghausenensis, closely related to A. fumigatus, was discovered, yet its virulence potential remains unclear. This study investigates inter- and intraspecies variation in phenotypic traits and transcriptomic responses to stress conditions relevant for human infection, using the previously researched A. oerlinghausenensis strain CBS139183 and three additional strains (8E048, 8E049, 8E050), compared to A. fumigatus strains Af293 and C30-NRZ-2017-546. Phenotypic assays revealed notable diversity in oxidative, heat, and hypoxic stress responses, with A. oerlinghausenensis CBS139183 consistently underperforming, while strains 8E048 and 8E049 demonstrated similar growth patterns to pathogenic A. fumigatus Af293. Transcriptomic analysis under stress conditions further supported this pattern, with 8E048 and 8E050 exhibiting transcriptional profiles distinct from CBS139183 but closely aligned with each other, particularly under heat and hypoxia. Differences in oxidative stress responses suggest strain-specific regulatory adaptations potentially influencing the ability to survive attacks from the immune system. Importantly, discrepancies between gene expression and phenotypic outcomes emphasize the complexity of fungal stress adaptation mechanisms. These findings challenge the use of single strain reference models to represent an entire species and highlight the necessity for approaches that encompasses the wide interspecies variety of pathogenic fungi. Our results suggest that some A. oerlinghausenensis strains may exhibit stress resilience and potential virulence profiles more similar to pathogenic A. fumigatus than previously assumed, warranting further investigation into their clinical relevance and evolutionary trajectories.