Integrated multi-omics identifies pathways governing interspecies interaction between A. fumigatus and K. pneumoniae

Abstract

Polymicrobial co- and superinfections involving bacterial and fungal pathogens pose serious challenges for diagnosis and therapy, and are associated with elevated morbidity and mortality. However, the metabolic dynamics of bacterial–fungal interactions (BFI) and the resulting impact on disease outcome remain largely unknown. The fungus Aspergillus fumigatus and the bacterium Klebsiella pneumoniae are clinically important pathogens sharing common niches in the human body, especially in the lower respiratory tract. We have exploited an integrated multi-omics approach to unravel the complex and multifaceted processes implicated in the interspecies communication involving these pathogens in mixed biofilms. In this setting, A. fumigatus responds to the bacterial challenge by rewiring its metabolism, attenuating the translational machineries, and by connecting secondary with primary metabolism, while K. pneumoniae maintains its central metabolism and translation activity. The flexibility in the metabolism of A. fumigatus and the ability to quickly adapt to the changing microenvironment mediated by the bacteria highlight new possibilities for studying the impact of cross-communication between competing interaction partners. The data underscore the complexity governing the dynamics underlying BFI, such as pronounced metabolic changes mounted in A. fumigatus interacting with K. pneumoniae. Our findings identify candidate biomarkers potentially exploitable for improved clinical management of BFI. A multi-omics study highlights the flexibility in the metabolism of Aspergillus fumigatus in microenvironments co-shared with Klebsiella pneumoniae, uncovering potential biomarkers to enhance clinical care for polymicrobial infections.