CONICET | Buscador de Institutos y Recursos Humanos

Copper (Cu) is an essential metal required as a cofactor in numerous essential biochemical reactions. However, free Cu ions can be toxic. In Gramnegative bacteria, Cu toxicity is handled by the cue regulon. This includes the Cu-sensor/regulator CueR that induces the expression of the Cu-efflux pump copA and the multicopper oxidase cueO coding genes. Under anaerobic conditions most species also require the Cus system to cope with Cu excess. This includes CusR/CusS, a two-component system that senses periplasmic Cu and induces the expression of CusCFBA, an RND-based Cuefflux pump that is responsible for the periplasmic homeostasis of the metal ion. In Salmonella as well as in other species that do not harbor the cus locus, Cu resistance in anaerobiosis relies on CueP, a periplasmic protein encoded by a gene that belongs to the Salmonella cue regulon. We have previously demonstrated that CueP can functionally replace the Cus complex for periplasmic copper resistance, in particular under anaerobic conditions. In this work, we examined the transcriptional regulation of the Salmonella cue regulon in different environments and found a differential expression within its constituents that affect in particular the expression of cueP. Using bioinformatics we detected a putative cis-acting sequence within the promoter of cueP that was likely responsible for this differential expression. In vivo transcription as well as in vitro footprinting experiments allowed us to confirm the existence of this regulatory element that is sensitive to the periplasmic stress caused by Cu excess. Phenotypic analysis allowed us to demonstrate that this periplasmic-stress element act in concert with CueR to ensure the correct supply of the components of the cue regulon when the environment becomes unfavorable for cell survival.