Abstract
The metal-specific CzcRS two-component system in Pseudomonas aeruginosa is involved in the repression of the OprD porin, causing in turn carbapenem antibiotic resistance in the presence of high zinc concentration. It has also been shown that CzcR is able to directly regulate the expression of multiple genes including virulence factors. CzcR is therefore an important regulator connecting (i) metal response, (ii) pathogenicity and (iii) antibiotic resistance in P. aeruginosa. Recent data have suggested that other regulators could negatively control oprD expression in the presence of zinc. Here we show that the RNA chaperone Hfq is a key factor acting independently of CzcR for the repression of oprD upon Zn treatment. Additionally, we found that an Hfq-dependent mechanism is necessary for the localization of CzcR to the oprD promoter, mediating oprD transcriptional repression. Furthermore, in the presence of Cu, CopR, the transcriptional regulator of the CopRS two-component system also requires Hfq for oprD repression. Altogether, these results suggest important roles for this RNA chaperone in the context of environment-sensing and antibiotic resistance in P. aeruginosa.
Highlights
Pseudomonas aeruginosa is an opportunistic pathogen that causes serious and diverse infections in host organisms by producing a broad range of virulence factors [1]
We decided to further investigate this alternative mechanism and used the ∆czcRS mutant, deleted for the metal-specific two-component system (TCS), to analyze the abundance of OprD porin at different Zn concentrations in LB medium when cells are in early stationary phase, i.e., after 6 h of growth (Figure 1A)
To test whether Hfq contributes to CzcRS TCS function, we examined the amount of OprD porin in the Wild type (WT) strain and in the single hfq mutant
Summary
Pseudomonas aeruginosa is an opportunistic pathogen that causes serious and diverse infections in host organisms by producing a broad range of virulence factors [1] This bacterium carries intrinsic resistances to multiple classes of antimicrobial compounds, representing a major challenge for the treatment of Pseudomonas’ infections [2]. The presence of an excess of these elements activates the metal-inducible CzcRS two-component system (TCS) that induces the expression of a metal efflux pump. It down-regulates the production of the OprD porin, rendering cells resistant to both trace metals and carbapenems. Cu has been shown to induce expression of the copRS
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