The Inactivation of the Putative Two-Component System Sensor PA14_27940 Increases the Susceptibility to Several Antibiotics and Reduces the Motility of .

The identification of targets whose inactivation increases the activity of antibiotics helps to fight antibiotic resistance. Previous work showed that a transposon-insertion mutant in the gene increases susceptibility to aminoglycosides. Since polar effects may affect the phenotype, in the present work, we generated an in-frame deletion mutant. A deletion increased the susceptibility to aminoglycosides, tetracycline, tigecycline, erythromycin and fosfomycin. Excepting fosfomycin, the other antibiotics are inducers of the MexXY efflux pump. MexXY induction is required for resistance to these antibiotics, which is post-transcriptionally regulated by the anti-repressor ArmZ. Although is inducible by tobramycin in Δ, the induction level is lower than in the parental PA14 strain. Additionally, is induced by tobramycin in PA14 and not in Δ, supporting that Δ presents an ArmZ-mediated defect in induction. For its part, hypersusceptibility to fosfomycin may be due to a reduced expression of and , which encode enzymes of the peptidoglycan recycling pathway. Δ also presents defects in motility, an element with relevance in 's virulence. Overall, our results support that PA14_27940 is a good target for the search of adjuvants that will increase the activity of antibiotics and reduce the virulence of .