Transcriptional control of a Salmonella-specific copper-resistance locus coding for thioredoxin-like proteins

LOPEZ MC; CHECA SK; SONCINI FC

Rosario

Congreso; 50th Annual Meeting; 2014

Sociedad Argentina de Bioquímica y Biología Molecular

Oxidoreductases of the thioredoxin superfamily contribute to Salmonella enterica serovar Typhimurium invasiveness and the virulence. The thioredoxin (TrxA) and the disulfide bond (Dsb) systems maintain proper periplasmic protein disulphide bond formation. Unlike E. coli, S. Typhimurium has species-specific thioredoxin-like proteins encoded in the suppressor of copper sensitivity (scs) operon. We observed that expression of the scsABCD operon is induced in the presence of copper (Cu), an essential micronutrient, that can induce oxidative stress at high concentrations. In fact, a mutant deleted of the whole scs operon is more sensitive to Cu than the wild-type strain, but not to other metal ions or oxidative stress inducers. Using bioinformatics as well as genetic approaches, we found that scsABCD transcription is regulated by major regulatory systems controlling envelope stress. In vitro and in vivo analyses indicated that at least one of these transcriptional factors directly interacts with the scs promoter. These analyses also allowed us to define a region that negatively controls scsABCD transcription. We proposed that this complex control of scsABCD transcription is required to increase Salmonella survival under severe Cu intoxication, both within host?s tissues and in the environment.