Virulence-Linked Mutations in Rubredoxin Reductase and Glutaredoxin: Impact on Antibiotic Susceptibility and Phage Therapy in <i>Pseudomonas aeruginosa</i>

Abstract

Pseudomonas aeruginosa (PAO1) is an opportunistic pathogen, lethal in immunocompromised individuals. The clinical management of PAO1 infections still depends deeply on antibiotic therapy. However, this therapy has been alarmingly overpowered by growing bacterial resistance mechanisms over the years. One of these bacterial mechanisms is quorum sensing (QS). QS is involved in the production of biofilm, rhamnolipids and pyocyanin, among other factors. The present study aimed to study the effect of the mutations in the genes of rubredoxin (Rub A1 and Rub A2) and glutaredoxin (GLRx) in the production of virulence traits and susceptibility of PAO1 to the antibiotic ciprofloxacin (CIP) and to infection by a phage cocktail. Rub A1, Rub A2, and GLRx showed a decrease in the expression of genes lasI, lasR, mvfR, and rpsL when compared to the wild type, PAO1. Rub A1 and Rub A2 also showed a decrease in the expression of the gene pqsA, while the mutant GLRx showed an increase of over 200% in expression compared to PAO1. The biofilm produced by the mutants Rub A1, Rub A2, and GLRx increased more than 1.5 times in comparison to PAO1, with statistical significance (p p p p < 0.0001), observed in the decrease in the absorbance values. These results may highlight the relevance of the genes Rub A1, Rub A2, and GLRX in the proliferation and treatment of infections with PAO1. Overall, this study gives preliminary insights into how gene expression may be helpful in strategies to overcome antibiotic resistance.

Keywords

• quorum sensing
• oxidative stress
• antibiotic stress
• biofilm production
• virulence