Uncovering the anaerobic copper-resistance pathway in Salmonella

LUCAS B. PONTEL; FERNANDO C. SONCINI

Villa Carlos Paz, Córdoba, Argentina

Congreso; XLIV Reunión anual; 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Copper resistance in Gram-negative bacteria is primarily controlled by the <i>cue</i> regulon. This regulon is composed by the Cu(I) sensor/regulator CueR that induces the expression of two target genes, <i>copA</i> and <i>cueO</i>, coding for an integral inner-membrane Cu-transporting P-type ATPase, and a periplasmic multicopper-Cu(I) oxidase, respectively. <i>Escherichia coli</i> also relies on the <i>cus</i> system to increase copper resistance under anaerobic conditions. Interestingly, <i>Salmonella</i> harbours all the <i>cue</i> components but lacks the <i>cus</i> locus. Despite of this, <i>Salmonella</i> displays higher resistance to copper than <i>E. coli</i> in anaerobic conditions. We have uncovered a novel CueR-regulated gene, named <i>cueP</i>, coding for a protein that increases resistance to copper both in aerobic and anaerobic conditions. CueP overexpression partially restored resistance to copper in a <i>cueO</i> deleted strain. To test whether CueP could functionally substitute the <i>E. coli cus</i> system for copper resistance, we replaced the entire <i>E. coli</i> chromosomal <i>cus</i> locus for the wild-type copy of the <i>Salmonella cueP</i>, including its own promoter. CueR-dependent expression of <i>cueP</i> increased resistance to copper in this engineered strain. Our results indicate that in contrast to other enterobacterial species <i>Salmonella</i> has evolved a single pathway to respond to copper excess both in aerobic and anaerobic conditions.