Lecture 11: Pseudomonas aeruginosa and Cystic Fibrosis Flashcards
What is the genetic cause of CF, and how does it affect the airways?
Cause: Autosomal recessive mutation in CFTR gene (chromosome 7) → defective Cl⁻ transport.
Effect: Thick, dehydrated mucus → impaired mucociliary clearance → chronic infections.
List 3 impaired defenses in CF airways.
Mucus plugging: Traps bacteria (e.g., P. aeruginosa).
TLR dysregulation: ↑TLR2 (hyperinflammation), ↓TLR4 (reduced LPS detection).
Neutrophil dysfunction: Excessive elastase degrades complement/sIgA.
Name 4 virulence factors and their roles.
Flagella: Adhesion to mucin; activates TLR5 (lost in chronic infection).
Pyocyanin: Inhibits cilia, induces neutrophil apoptosis.
Elastase B: Degrades ECM, lysozyme, sIgA.
Biofilm: Alginate-rich matrix → antibiotic resistance.
How does P. aeruginosa acquire iron in CF airways?
Produces siderophores (pyoverdine/pyochelin) to steal Fe³⁺ from host transferrin/lactoferrin.
Why are biofilms problematic in CF?
Protection: Shields bacteria from neutrophils/antibiotics.
Phenotype shift: Mucoid alginate overproduction → chronic infection.
Compare P. aeruginosa in early vs. chronic CF infection.
Early: Motile, virulent, antibiotic-sensitive.
Chronic: Mucoid, reduced virulence, hypermutator (antibiotic-resistant).
How is P. aeruginosa identified in the lab?
Culture: Pseudomonas Isolation Agar (pyocyanin pigment; cetrimide/nalidixic acid selective).
Microscopy: Gram-negative rods.
Why is P. aeruginosa hard to treat in CF?
Biofilm resistance: Limits antibiotic penetration.
Hypermutation: Rapid resistance development (e.g., to tobramycin).
How does neutrophil elastase (NE) worsen CF?
NE → ↑IL-8 → recruits more neutrophils → tissue damage → chronic inflammation.
What % of adult CF patients develop chronic P. aeruginosa infections?
~44.5% (vs. 5.4% in pediatric patients).
