Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis
Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion a...
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2025-06-01
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| author | Dayana Borisova Tsvetelina Paunova-Krasteva Tanya Strateva Stoyanka Stoitsova |
| author_facet | Dayana Borisova Tsvetelina Paunova-Krasteva Tanya Strateva Stoyanka Stoitsova |
| author_sort | Dayana Borisova |
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| description | Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and fluid homeostasis. Dysfunctional CFTR disrupts mucociliary clearance, particularly in the respiratory tract, resulting in persistent bacterial colonization, chronic inflammation, and progressive pulmonary damage—ultimately leading to respiratory failure, the principal cause of mortality in CF patients. Early diagnosis and advances in therapy have substantially improved both survival and quality of life. A hallmark of CF pathology is the establishment of polymicrobial infections within the thickened airway mucus. <i>Pseudomonas aeruginosa</i> is the dominant pathogen in chronic CF lung infections and demonstrates a remarkable capacity for adaptation via biofilm formation, metabolic reprogramming, and immune evasion. Biofilms confer increased tolerance to antimicrobial agents and facilitate long-term persistence in hypoxic, nutrient-limited microenvironments. <i>P. aeruginosa</i> exhibits a wide range of virulence factors, including exotoxins (e.g., ExoU, ExoS), pigments (pyoverdine, pyochelin), and motility structures (flagella and pili), which contribute to tissue invasion, immune modulation, and host damage. During chronic colonization, <i>P. aeruginosa</i> undergoes significant genotypic and phenotypic changes, such as mucoid conversion, downregulation of acute virulence pathways, and emergence of hypermutator phenotypes that facilitate rapid adaptation. Persistent cells, a specialized subpopulation characterized by metabolic dormancy and antibiotic tolerance, further complicate eradication efforts. The dynamic interplay between host environment and microbial evolution underlies the heterogeneity of CF lung infections and presents significant challenges for treatment. Elucidating the molecular mechanisms driving persistence, hypermutability, and biofilm resilience is critical for the development of effective therapeutic strategies targeting chronic <i>P. aeruginosa</i> infections in CF. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-8ba7dac9e1a24429a54cf4dc2a8abd242025-08-20T03:56:49ZengMDPI AGMicroorganisms2076-26072025-06-01137152710.3390/microorganisms13071527Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and PathogenesisDayana Borisova0Tsvetelina Paunova-Krasteva1Tanya Strateva2Stoyanka Stoitsova3Stephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113 Sofia, BulgariaStephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113 Sofia, BulgariaDepartment of Medical Microbiology “Corr. Mem. Prof. Ivan Mitov, MD, DMSc”, Faculty of Medicine, Medical University of Sofia, 2 Zdrave Str., 1431 Sofia, BulgariaStephan Angeloff Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 25, 1113 Sofia, BulgariaCystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and fluid homeostasis. Dysfunctional CFTR disrupts mucociliary clearance, particularly in the respiratory tract, resulting in persistent bacterial colonization, chronic inflammation, and progressive pulmonary damage—ultimately leading to respiratory failure, the principal cause of mortality in CF patients. Early diagnosis and advances in therapy have substantially improved both survival and quality of life. A hallmark of CF pathology is the establishment of polymicrobial infections within the thickened airway mucus. <i>Pseudomonas aeruginosa</i> is the dominant pathogen in chronic CF lung infections and demonstrates a remarkable capacity for adaptation via biofilm formation, metabolic reprogramming, and immune evasion. Biofilms confer increased tolerance to antimicrobial agents and facilitate long-term persistence in hypoxic, nutrient-limited microenvironments. <i>P. aeruginosa</i> exhibits a wide range of virulence factors, including exotoxins (e.g., ExoU, ExoS), pigments (pyoverdine, pyochelin), and motility structures (flagella and pili), which contribute to tissue invasion, immune modulation, and host damage. During chronic colonization, <i>P. aeruginosa</i> undergoes significant genotypic and phenotypic changes, such as mucoid conversion, downregulation of acute virulence pathways, and emergence of hypermutator phenotypes that facilitate rapid adaptation. Persistent cells, a specialized subpopulation characterized by metabolic dormancy and antibiotic tolerance, further complicate eradication efforts. The dynamic interplay between host environment and microbial evolution underlies the heterogeneity of CF lung infections and presents significant challenges for treatment. Elucidating the molecular mechanisms driving persistence, hypermutability, and biofilm resilience is critical for the development of effective therapeutic strategies targeting chronic <i>P. aeruginosa</i> infections in CF.https://www.mdpi.com/2076-2607/13/7/1527cystic fibrosis<i>Pseudomonas aeruginosa</i>biofilmsvirulence factorsantibioticspersistence |
| spellingShingle | Dayana Borisova Tsvetelina Paunova-Krasteva Tanya Strateva Stoyanka Stoitsova Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis Microorganisms cystic fibrosis <i>Pseudomonas aeruginosa</i> biofilms virulence factors antibiotics persistence |
| title | Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis |
| title_full | Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis |
| title_fullStr | Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis |
| title_full_unstemmed | Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis |
| title_short | Biofilm Formation of <i>Pseudomonas aeruginosa</i> in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis |
| title_sort | biofilm formation of i pseudomonas aeruginosa i in cystic fibrosis mechanisms of persistence adaptation and pathogenesis |
| topic | cystic fibrosis <i>Pseudomonas aeruginosa</i> biofilms virulence factors antibiotics persistence |
| url | https://www.mdpi.com/2076-2607/13/7/1527 |
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