Impact of D-amino acid dehydrogenase on virulence factor production by a Pseudomonas aeruginosa
Kathryn E Oliver1, Laura Silo-Suh
1a Department of Biological Sciences, Auburn University, Auburn, AL 36849, USA.
Abstract:
Chronic Pseudomonas aeruginosa infections remain the leading cause of lung dysfunction and mortality for cystic fibrosis (CF) patients. Many other bacteria inhabit the CF lung, but P. aeruginosa utilizes novel strategies that allow it to colonize this environment as the predominant bacterial pathogen. D-Amino acid dehydrogenase encoded by dadA is highly expressed by P. aeruginosa within the CF lung, and it is required for optimal production of hydrogen cyanide by some CF-adapted isolates. To better understand the increased significance of D-amino acid dehydrogenase in P. aeruginosa physiology, we characterized the contribution of the dad operon to virulence factor production. In this study, we determined that DadA is required for optimal production of pyocyanin, pyoverdine, and rhamnolipid by CF-adapted and non-CF-adapted isolates of P. aeruginosa. In addition, DadA is required for optimal production of alginate, biofilm formation, and virulence of a CF-adapted isolated of P. aeruginosa in an alfalfa seedling model of infection. Taken together, the results indicate that DadA plays a pleiotropic role in the production of important virulence factors by P. aeruginosa.
Insights
D-amino acid dehydrogenase (DadA) is crucial for Pseudomonas aeruginosa virulence in cystic fibrosis (CF) lungs. This enzyme supports the production of key toxins, biofilm formation, and overall infection severity.
Area of Science:
- Microbiology
- Infectious Diseases
- Biochemistry
Background:
- Chronic Pseudomonas aeruginosa infections are the primary cause of mortality in cystic fibrosis (CF) patients.
- P. aeruginosa employs unique strategies to thrive as the dominant pathogen in the CF lung environment.
- The D-amino acid dehydrogenase (dadA) gene is highly expressed in P. aeruginosa within CF lungs.
Purpose of the Study:
- To investigate the role of the dad operon in Pseudomonas aeruginosa virulence factor production.
- To understand the physiological significance of D-amino acid dehydrogenase (DadA) in P. aeruginosa.
Main Methods:
- Characterization of the dad operon's contribution to virulence factor production.
- Assessment of DadA's role in pyocyanin, pyoverdine, and rhamnolipid production.
- Evaluation of DadA's impact on alginate production, biofilm formation, and virulence in a CF-adapted P. aeruginosa isolate using an alfalfa seedling model.
Main Results:
- DadA is essential for optimal production of pyocyanin, pyoverdine, and rhamnolipid in both CF-adapted and non-CF-adapted P. aeruginosa isolates.
- DadA is required for enhanced alginate production and biofilm formation in CF-adapted P. aeruginosa.
- DadA significantly contributes to the virulence of CF-adapted P. aeruginosa in a plant-based infection model.
Conclusions:
- D-amino acid dehydrogenase (DadA) plays a multifaceted role in the production of critical virulence factors by Pseudomonas aeruginosa.
- DadA influences the production of toxins, exopolysaccharides, and biofilm formation, impacting P. aeruginosa's pathogenicity in CF.
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