A consortium of regulatory systems controls the expression of a Salmonella-specific efflux complex

SEBASTIÁN CERMINATI; SUSANA K. CHECA; FERNANDO C. SONCINI

Mendoza

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2012

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

CBA efflux systems are tripartite protein complexes that direct export of metal ions, xenobiotics or drugs either from the cytoplasm, the inner membrane or the periplasm into the extracellular space. GesABC is one of the five Salmonella CBA efflux pumps. Its transcription is controlled by the Au-sensor GolS. Among the three transcriptional units controlled by GolS, gesABC has the most divergent GolS-dependent operator, resulting in its delayed expression in the presence of Au ions. Besides its essential role in Au-resistance, the GesABC system can also mediate resistance to different drugs in a strain deleted in the main drug transporter AcrAB, suggesting additional roles for cell detoxification. Using bioinformatics we identified putative cis-acting regulatory sequences recognized by global as well as stress-induced transcriptional regulatory systems that would control the expression of the efflux pump under different conditions. Their effective control of gesABC expression was verified by reporter expression on strains deleted in different regulators. Specific recognition by these systems was confirmed by in vitro assays. Our results indicate that a regulatory systems’ consortium controls the expression of gesABC, providing the proper supply of the efflux complex according to the quality and severity of different stress conditions that the pathogen encounters.