Elizabeth B Burgener, Pamela Cai, Michael J Kratochvil, Laura S Rojas-Hernandez, Nam Soo Joo, Aditi Gupta, Patrick R Secor, Sarah C Heilshorn, Andrew J Spakowitz, Jeffrey J Wine, Paul L Bollyky, Carlos E Milla
{"title":"溶解性丝状假单胞菌噬菌体噬菌体 Pf 可减缓粘膜运输速度","authors":"Elizabeth B Burgener, Pamela Cai, Michael J Kratochvil, Laura S Rojas-Hernandez, Nam Soo Joo, Aditi Gupta, Patrick R Secor, Sarah C Heilshorn, Andrew J Spakowitz, Jeffrey J Wine, Paul L Bollyky, Carlos E Milla","doi":"10.1093/pnasnexus/pgae390","DOIUrl":null,"url":null,"abstract":"Pseudomonas aeruginosa is a major pulmonary pathogen causing chronic pulmonary infections in people with Cystic Fibrosis (CF). The P. aeruginosa filamentous and lysogenic bacteriophage, Pf phage, is abundant in the airways of many people with CF and has been associated with poor outcomes in a cross-sectional cohort study. Previous studies have identified roles for Pf phage in biofilm formation, specifically forming higher-order birefringent, liquid crystals when in contact with other biopolymers in biofilms. Liquid crystalline biofilms are more adherent and viscous than those with out liquid crystals. A key feature of biofilms to enhance bacterial adherence and resist physicial clearance. The effect of Pf phage on mucociliary transport is unknown. We found that primary CF and non-CF nasal epithelial cells cultured at air liquid interface treated with Pf phage exhibit liquid crystalline structures in the overlying mucus. On these cell cultures, Pf phage entangles cilia but does not affect ciliary beat frequency. In both these in vitro cell cultures and in an ex vivo porcine trachea model introduction of Pf phage decreases mucociliary transport velocity. Pf phage also blocks the rescue of mucociliary transport by cystic fibrosis transmembrane conductance regulator modulators in CF cultures. Thus, Pf phage may contribute to the pathogenesis of P. aeruginosa-associated CF lung disease via induction of liquid crystalline characteristics to airway secretions, leading to impaired mucociliary transport. Targeting Pf phage may be useful in treatment CF as well as other settings of chronic P. aeruginosa infections.","PeriodicalId":516525,"journal":{"name":"PNAS Nexus","volume":"78 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The lysogenic filamentous Pseudomonas bacteriophage phage Pf slows mucociliary transport\",\"authors\":\"Elizabeth B Burgener, Pamela Cai, Michael J Kratochvil, Laura S Rojas-Hernandez, Nam Soo Joo, Aditi Gupta, Patrick R Secor, Sarah C Heilshorn, Andrew J Spakowitz, Jeffrey J Wine, Paul L Bollyky, Carlos E Milla\",\"doi\":\"10.1093/pnasnexus/pgae390\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Pseudomonas aeruginosa is a major pulmonary pathogen causing chronic pulmonary infections in people with Cystic Fibrosis (CF). The P. aeruginosa filamentous and lysogenic bacteriophage, Pf phage, is abundant in the airways of many people with CF and has been associated with poor outcomes in a cross-sectional cohort study. Previous studies have identified roles for Pf phage in biofilm formation, specifically forming higher-order birefringent, liquid crystals when in contact with other biopolymers in biofilms. Liquid crystalline biofilms are more adherent and viscous than those with out liquid crystals. A key feature of biofilms to enhance bacterial adherence and resist physicial clearance. The effect of Pf phage on mucociliary transport is unknown. We found that primary CF and non-CF nasal epithelial cells cultured at air liquid interface treated with Pf phage exhibit liquid crystalline structures in the overlying mucus. On these cell cultures, Pf phage entangles cilia but does not affect ciliary beat frequency. In both these in vitro cell cultures and in an ex vivo porcine trachea model introduction of Pf phage decreases mucociliary transport velocity. Pf phage also blocks the rescue of mucociliary transport by cystic fibrosis transmembrane conductance regulator modulators in CF cultures. Thus, Pf phage may contribute to the pathogenesis of P. aeruginosa-associated CF lung disease via induction of liquid crystalline characteristics to airway secretions, leading to impaired mucociliary transport. Targeting Pf phage may be useful in treatment CF as well as other settings of chronic P. aeruginosa infections.\",\"PeriodicalId\":516525,\"journal\":{\"name\":\"PNAS Nexus\",\"volume\":\"78 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PNAS Nexus\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/pnasnexus/pgae390\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PNAS Nexus","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/pnasnexus/pgae390","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
The lysogenic filamentous Pseudomonas bacteriophage phage Pf slows mucociliary transport
Pseudomonas aeruginosa is a major pulmonary pathogen causing chronic pulmonary infections in people with Cystic Fibrosis (CF). The P. aeruginosa filamentous and lysogenic bacteriophage, Pf phage, is abundant in the airways of many people with CF and has been associated with poor outcomes in a cross-sectional cohort study. Previous studies have identified roles for Pf phage in biofilm formation, specifically forming higher-order birefringent, liquid crystals when in contact with other biopolymers in biofilms. Liquid crystalline biofilms are more adherent and viscous than those with out liquid crystals. A key feature of biofilms to enhance bacterial adherence and resist physicial clearance. The effect of Pf phage on mucociliary transport is unknown. We found that primary CF and non-CF nasal epithelial cells cultured at air liquid interface treated with Pf phage exhibit liquid crystalline structures in the overlying mucus. On these cell cultures, Pf phage entangles cilia but does not affect ciliary beat frequency. In both these in vitro cell cultures and in an ex vivo porcine trachea model introduction of Pf phage decreases mucociliary transport velocity. Pf phage also blocks the rescue of mucociliary transport by cystic fibrosis transmembrane conductance regulator modulators in CF cultures. Thus, Pf phage may contribute to the pathogenesis of P. aeruginosa-associated CF lung disease via induction of liquid crystalline characteristics to airway secretions, leading to impaired mucociliary transport. Targeting Pf phage may be useful in treatment CF as well as other settings of chronic P. aeruginosa infections.