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CF airway infections are polymicrobial airway ecosystems often dominated by CF pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia, Stenotrophomonas, Achromobacter, and nontuberculous mycobacteria that drive cycles of infection, inflammation, and bronchiectasis. Highly effective CFTR modulators, including elexacaftor\/tezacaftor\/ivacaftor, improve airway hydration and mucociliary clearance and reduce pathogen CF acquisition and density. However, even with CFTR modulator treatment, most individuals with established infection remain chronically infected, and long-term impacts of CFTR modulators on airway infection dynamics and associated clinical outcomes remain unclear. In this review, we address key gaps in understanding chronic infection in the CFTR modulator era, including changes in infection-related lung disease pathogenesis, airway\u2013gut microbiome interactions, approaches to airway infection sampling, and implications for infection management.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf626","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T13:17:36Z","timestamp":1765372656000},"page":"631-639","source":"Crossref","is-referenced-by-count":4,"title":["Microbiota, Mucus, and Modulators: Cystic Fibrosis Infection Pathogenesis in the Cystic Fibrosis Transmembrane Conductance Regulator Modulator Era"],"prefix":"10.1093","volume":"233","author":[{"given":"Christina S","family":"Thornton","sequence":"first","affiliation":[{"name":"Division of Respiratory Medicine, Departments of Medicine and Microbiology, Immunology and Infectious Diseases, University of Calgary , Calgary, Alberta 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