Related Experiment Videos
Pseudomonas aeruginosa from patients with cystic fibrosis affects function of pulmonary surfactant
1Department of Gynecology/Obstetrics, State University of New York at Buffalo, 14222, USA.
Abstract:
Patients with cystic fibrosis are severely affected by an infection with Pseudomonas aeruginosa, a microbe known to synthesize phospholipase C. This study was designed to determine whether that enzyme would affect the function of pulmonary surfactant phospholipids. Mucoid and nonmucoid strains of P. aeruginosa, freshly obtained from patients with cystic fibrosis, were cultured for 12 h on agar plates. The bacteria were suspended in saline solution and then pelleted by centrifugation. The supernatant was used to dilute the surfactant preparation, calf lung surfactant extract, from 35 to 2 mg/mL. Surfactant function, before and after incubation, was examined with a capillary surfactometer, an instrument specifically developed for an evaluation of the ability of surfactant to maintain patency of a narrow glass tube, simulating a terminal conducting airway. Phospholipid hydrolysis was also evaluated biochemically by determining the total content of phospholipids in surfactant before and after incubation. In five experiments, the lipids were separated with thin-layer chromatography, and the phosphorus content was determined in the diacylphosphatidylcholine band before and after incubation for 6, 24, and 48 h. Capillary openness and phospholipid concentration decreased as enzyme concentration and time of incubation increased (p<0.0001). Linear regression showed a significant correlation between time of capillary openness and phospholipid concentration (r = 0.957; p<0.0001). Calf lung surfactant extract hydrolysis was catalyzed by extracts of the bacteria, particularly the nonmucoid, analogous to the catalysis observed with phospholipase C. Surfactant hydrolysis catalyzed by enzymes from P. aeruginosa might severely affect surfactant function provided enzyme concentration is high and time of incubation is long.
Insights
Pseudomonas aeruginosa phospholipase C degrades pulmonary surfactant phospholipids, impairing lung function in cystic fibrosis patients. This enzyme
Area of Science:
- Pulmonary Medicine
- Microbiology
- Biochemistry
Background:
- Cystic fibrosis patients suffer severe lung infections from Pseudomonas aeruginosa.
- Pseudomonas aeruginosa produces phospholipase C, an enzyme with potential to degrade lung surfactant.
Purpose of the Study:
- To investigate the effect of Pseudomonas aeruginosa phospholipase C on pulmonary surfactant phospholipids.
- To determine if bacterial phospholipase C impacts surfactant function in a model simulating lung airways.
Main Methods:
- Cultured mucoid and nonmucoid P. aeruginosa strains from cystic fibrosis patients.
- Used bacterial supernatant containing phospholipase C to incubate calf lung surfactant extract.
- Assessed surfactant function using a capillary surfactometer and measured phospholipid hydrolysis biochemically.
- Quantified phospholipid content, specifically diacylphosphatidylcholine, after incubation using thin-layer chromatography.
Main Results:
- Capillary openness and phospholipid concentration significantly decreased with increasing enzyme concentration and incubation time (p<0.0001).
- A strong positive correlation was found between capillary openness duration and phospholipid concentration (r=0.957; p<0.0001).
- Bacterial extracts, particularly from nonmucoid strains, catalyzed surfactant hydrolysis, similar to purified phospholipase C.
Conclusions:
- Phospholipase C from Pseudomonas aeruginosa can hydrolyze pulmonary surfactant phospholipids.
- This hydrolysis may significantly impair surfactant function, especially at high enzyme concentrations and prolonged incubation times.
- The findings suggest a potential mechanism for lung dysfunction in cystic fibrosis patients due to Pseudomonas aeruginosa infection.