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Visualization of Pseudomonas aeruginosa within the Sputum of Cystic Fibrosis Patients
Published on: July 16, 2020
Surfactant Protein A Recognizes Outer Membrane Protein OprH on Pseudomonas aeruginosa Isolates From Individuals With
Mohammad Qadi1, Carla Lopez-Causapé2,3, Sofia Izquierdo-Rabassa1
1Instituto Universitario de Investigación en Ciencias de la Salud, Universidad de las Islas Baleares.
Abstract:
Surfactant protein A (SP-A) plays a critical role in the clearance of Pseudomonas aeruginosa from the lung. However, there is limited information about the interaction of this protein with P. aeruginosa isolates from individuals with cystic fibrosis (CF). We characterized the interplay between SP-A and a collection of isogenic sequential isolates from 7 patients with CF. We identified outer membrane protein OprH as a novel ligand for SP-A on P. aeruginosa The last-available (late) isolates from patients with CF bound significantly less SP-A than their respective first-available (early) isolates. This difference could be associated with a reduction in the expression of OprH. Binding of SP-A to OprH promoted phagocytic killing; thus, late CF isolates were at least 2-fold more resistant to SP-A-mediated killing by human macrophages than their respective early isolates. We postulate that the reduction of OprH expression is a previously unrecognized adaptation of P. aeruginosa to the lung of individuals with CF that facilitates the escape of the microorganism from SP-A-mediated phagocytic killing.
Insights
Pseudomonas aeruginosa in cystic fibrosis (CF) lungs reduces outer membrane protein OprH. This adaptation helps bacteria evade surfactant protein A (SP-A) immune clearance by macrophages.
Area of Science:
- Pulmonary immunology
- Microbial pathogenesis
- Cystic Fibrosis research
Background:
- Surfactant protein A (SP-A) is crucial for clearing Pseudomonas aeruginosa from the lungs.
- Limited data exists on SP-A interactions with P. aeruginosa isolates from cystic fibrosis (CF) patients.
Purpose of the Study:
- To investigate the interaction between SP-A and sequential P. aeruginosa isolates from CF patients.
- To identify bacterial factors influencing SP-A binding and subsequent immune evasion.
Main Methods:
- Characterization of isogenic sequential P. aeruginosa isolates from 7 CF patients.
- Identification of SP-A ligands on P. aeruginosa outer membrane.
- Assessment of SP-A binding affinity and SP-A-mediated phagocytic killing.
Main Results:
- Outer membrane protein OprH identified as a novel SP-A ligand.
- Late CF isolates exhibited significantly reduced SP-A binding compared to early isolates.
- Reduced OprH expression correlated with decreased SP-A binding and increased resistance to SP-A-mediated killing.
Conclusions:
- Downregulation of OprH is a potential adaptation by P. aeruginosa in CF lungs.
- This adaptation allows bacteria to evade SP-A-mediated clearance by macrophages.
- Understanding this mechanism may reveal new therapeutic targets for CF lung infections.
