Researchers found that volatile organic compounds emitted by Pseudomonas aeruginosa trigger molecular pathways that disrupt airway mucus balance, according to a peer-reviewed study published in Nature Communications. The findings demonstrate that bacterial vapors increase the expression of the mucin MUC5AC at concentrations present in both bacterial culture headspace and the breath of cystic fibrosis patients.
Laboratory tests using air-liquid interface cultures of normal and diseased human bronchial epithelial cells alongside chronic exposure mouse models showed how the airborne compounds impair lung clearance. The bacterial chemicals activate aryl hydrocarbon receptor signaling, which suppresses FOXA2, a regulatory factor required for normal airway mucus homeostasis. Treatment with an AhR inhibitor successfully restored FOXA2 levels and attenuated excess mucin production.
Mechanistic analysis showed that the volatile compounds activate an AhR-ARNT-CYP1-ROS signaling cascade. This reaction sequence stimulates downstream EGFR-AKT and ERK signaling pathways, creating the hypersecretion and clearance failures commonly seen in chronic bacterial lung infections.
Tissue samples for the experiments came from the Lung Center Tissue Bank at Temple University and the Marsico Lung Institute and Cystic Fibrosis Center at the University of North Carolina at Chapel Hill. The authors also used 16HBE14o- cells originally provided by the University of California, San Francisco, with mouse lung histology prepared at the University of Illinois at Urbana-Champaign.
Gee W. Lau and Shanny Hsuan Kuo of the University of Illinois at Urbana-Champaign co-authored the paper with researchers from Temple University, the University of Washington, and Harvard Medical School. The United States National Institutes of Health supported the research through grant numbers R01HL142626 and R21AI171524A1.
