The survival rates of individuals with cystic fibrosis (CF) have significantly increased as a result of improved therapies, such as the inclusion of cystic fibrosis transmembrane conductance regulator (CFTR) modulators for some mutations. However, microbial infection of the airways remains a significant clinical problem. The well-known pathogens Pseudomonas aeruginosa and Staphylococcus aureus continue to establish difficult-to-treat infections in the CF lung. However, in recent years, there has been an increased prevalence of both Aspergillus fumigatus (Af) and non-tuberculous mycobacteria (NTM) species isolated from CF patient sputa. The emergence of these pathogens opens an important area of discussion about multikingdom infections, specifically, how interspecies interactions have the potential to shape the course of infection, such as tolerance to host immune defenses and antimicrobial therapies. Their ability to establish themselves in an existing polymicrobial environment suggests to us that microbial interactions play a significant role, and characterizing these mechanisms and understanding their implications will be critical to the future development of better antimicrobial therapies. With this minireview, we hope to inspire conversations about and demonstrate the merit of more research in this area.


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