Co-dependence on copper excess and periplasmic stress to control Salmonella cueP expression

PEZZA, A.; PONTEL, L. B.; SONCINI, F. C.

Rosario

Congreso; L Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Copper (Cu) is an essential metal required as cofactor in numerous biochemical reactions, and at the same time is highly toxic. In most Gram(-) bacteria Cu toxicity is handled by the cue regulon, that includes copA and cueO, coding for a Cu-efflux pump and a periplasmic multicopper oxidase, controlled by the cytoplasmic Cu-sensor/regulator CueR. Most species also rely on the Cus system to cope with bacterial envelope Cu excess. This includes a two-component system that senses periplasmic Cu and induces the expression of a periplasmic Cu-efflux system CusCFBA. Salmonella does not harbor the cus locus. Instead, a CueR-regulated gene coding for a periplasmic protein, CueP, substitutes the function of the Cus system. We observed a differential expression within the Salmonella cue regulon that particularly affects cueP expression. By site-directed mutagenesis we detected a cis-acting sequence within cueP promoter responsible for this differential expression. In vivo as well as in vitro experiments allowed us to confirm this regulatory element, sensitive to the periplasmic stress caused by Cu excess. Phenotypic analysis allowed us to demonstrate that this periplasmic-stress sensory element acts in concert with CueR to ensure the correct supply of this component of the cue regulon when the environment becomes unfavorable for survival.