Randomized trial demonstrates altered virulence and increased antimicrobial resistance in Pseudomonas aeruginosa mutants, suggesting new therapeutic targets.
Key Points
This study investigates the role of a gain-of-function mutation in CpxS on antimicrobial resistance and virulence in Pseudomonas aeruginosa.
Gain-of-function mutant generated by truncating the periplasmic sensing domain of CpxS.
Comparison of virulence traits and antimicrobial resistance between mutant PAO1:: cpxS Δ32-147 and wild-type PAO1.
Transcriptomic analysis to assess gene expression changes related to virulence pathways.
The mutant showed a 2- to 4-fold increase in antimicrobial resistance.
Virulence traits diminished: motility decreased by 44% (swimming) and 34% (swarming), and cytotoxicity against A549 cells reduced from 79.6% to 25.4% at MOI 100.
In a murine model, PAO1:: cpxS Δ32-147 resulted in only 10% lethality, compared to 100% for wild-type PAO1.