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Pseudomonas aeruginosa adherence to remodelling respiratory epithelium
S de Bentzmann1, P Roger, E Puchelle
1INSERM U314, CHR Maison Blanche, Reims, France.
Abstract:
Pseudomonas aeruginosa is an opportunistic organism, which frequently colonizes the respiratory tract of patients with impaired host defence. In cystic fibrosis (CF) patients, this pathogen causes a progressive destructive bronchitis and bronchiolitis and is responsible for high mortality. Normal respiratory epithelium is protected against bacteria via mucus and mucociliary clearance. Alteration of mucociliary clearance and of glycosylation of mucins in CF facilitates the access of bacteria to the underlying airway epithelial cells. Intact respiratory epithelium does not bind P. aeruginosa, whereas injured respiratory epithelium is highly susceptible to P. aeruginosa adherence. We found that the high affinity of respiratory epithelium, from CF and non-CF sources, for P. aeruginosa, during the wound repair process is related to the apical expression of asialo ganglioside M1 (aGM1). The affinity of repairing respiratory epithelium for P. aeruginosa is time-dependent, and is related to transient apical expression of aGM1 at the surface of repairing respiratory epithelial cells. CF respiratory epithelial cells apically express more aGM1 residues with relation to an increased affinity for P. aeruginosa than non CF cells. High epithelial damage followed by repair represents a major cause of P. aeruginosa adherence to airway epithelium in cystic fibrosis. However, P. aerurignosa adherence and colonization are not restricted to cystic fibrosis disease and P. aeruginosa pneumonia may also occur in severely immunocompromised patients, suggesting that epithelial injury and decreased host-response favour the colonization of the airways by P. aeruginosa.
Insights
Pseudomonas aeruginosa readily adheres to repairing airway epithelial cells, particularly in cystic fibrosis (CF) patients, due to increased asialo ganglioside M1 (aGM1) expression. This bacterial adherence mechanism highlights a key factor in CF lung disease progression.
Area of Science:
- Microbiology
- Cell Biology
- Pulmonary Medicine
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen that frequently colonizes the respiratory tract in individuals with compromised immune systems, notably cystic fibrosis (CF) patients.
- In CF, impaired mucociliary clearance and altered mucin glycosylation facilitate bacterial access to airway epithelial cells.
- Intact respiratory epithelium resists P. aeruginosa binding, while injured epithelium becomes highly susceptible.
Purpose of the Study:
- To investigate the mechanism of Pseudomonas aeruginosa adherence to airway epithelium, particularly during the wound repair process.
- To determine the role of asialo ganglioside M1 (aGM1) in P. aeruginosa binding to respiratory epithelial cells.
- To compare P. aeruginosa adherence in cystic fibrosis (CF) versus non-CF respiratory epithelial cells.
Main Methods:
- Analysis of P. aeruginosa adherence to respiratory epithelial cells from both CF and non-CF sources.
- Assessment of asialo ganglioside M1 (aGM1) expression on the apical surface of repairing epithelial cells.
- Time-dependent evaluation of epithelial cell affinity for P. aeruginosa.
Main Results:
- Respiratory epithelium exhibits high affinity for P. aeruginosa during wound repair, linked to apical asialo ganglioside M1 (aGM1) expression.
- This affinity is time-dependent, correlating with transient aGM1 expression on repairing epithelial cells.
- CF respiratory epithelial cells show higher aGM1 expression and increased P. aeruginosa affinity compared to non-CF cells.
Conclusions:
- Epithelial damage and subsequent repair, characterized by aGM1 upregulation, are major contributors to P. aeruginosa adherence in CF airways.
- While prominent in CF, P. aeruginosa colonization can also occur in immunocompromised patients, indicating that epithelial injury and reduced host defense favor airway colonization.
- Targeting aGM1-mediated adherence could be a potential therapeutic strategy for P. aeruginosa infections in the respiratory tract.