Metabolomic profiling reveals unique markers for Pseudomonas aeruginosa LasR deficiency
M Trinidad García-Barceló1,2, Rosa M Gomila2, Alex González-Alsina1
1Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.
Abstract:
Pseudomonas aeruginosa is a primary driver of morbidity and mortality in cystic fibrosis (CF) patients. Throughout the course of infection, P. aeruginosa undergoes significant evolution and adaptation to the dynamic environment of the CF respiratory tract, leading to the emergence of diverse phenotypes. Among the variants that arise during this process are mutations in the regulatory gene lasR. While clinical significance of LasR deficiency is well recognized, current evidence does not fully elucidate the metabolic changes associated with the absence of this master regulator. To address this, we conducted untargeted metabolic profiling of cell supernatants (exometabolomes) to compare twenty-four P. aeruginosa strains, collected over 3-8 years from ten CF patients classified either as LasR functional (LasR+) or LasR non-functional (LasR-). We found a highly significant relationship between the LasR phenotype and the global exometabolic profile of the clinical strains. Furthermore, our analysis identified several metabolites whose production appears to be linked to LasR expression. These findings were validated using a loss of function/gain of function approach. This connection between lasR genetic expression, the chronic adaptation of P.aeruginosa to the CF lung environment and the generation of traceable metabolic markers highlights a potential avenue for diagnosing and monitoring respiratory infections caused by this pathogen.
Insights
Pseudomonas aeruginosa in cystic fibrosis (CF) patients shows metabolic changes linked to the lasR gene. These metabolic markers could help diagnose and monitor CF lung infections.
Area of Science:
- Microbiology
- Metabolomics
- Infectious Diseases
Background:
- Pseudomonas aeruginosa is a major cause of illness and death in cystic fibrosis (CF) patients.
- P. aeruginosa adapts to the CF lung environment, leading to genetic mutations like those in the lasR gene.
- The metabolic impact of lasR gene mutations in CF infections is not fully understood.
Purpose of the Study:
- To investigate the metabolic differences in P. aeruginosa strains with functional (LasR+) and non-functional (LasR-) lasR genes from CF patients.
- To identify specific metabolic markers associated with lasR gene expression in chronic CF infections.
Main Methods:
- Untargeted metabolic profiling of exometabolomes from 24 P. aeruginosa strains.
- Comparison of strains from ten CF patients collected over 3-8 years.
- Validation using loss-of-function and gain-of-function experiments.
Main Results:
- A significant correlation was found between the LasR phenotype and the overall exometabolome profile of clinical P. aeruginosa strains.
- Several metabolites were identified as being significantly linked to lasR gene expression.
- Experimental validation confirmed the link between lasR and metabolite production.
Conclusions:
- The lasR gene status significantly influences the metabolic output of P. aeruginosa in the CF lung.
- Specific metabolites can serve as traceable markers for P. aeruginosa adaptation and infection in CF.
- This research offers a potential strategy for diagnosing and monitoring P. aeruginosa infections in CF patients.
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