Parallels and differences in copper resistance among enterobacterial species

LUCAS B. PONTEL; FERNANDO C. SONCINI

Rosario, Santa Fe, Argentina

Congreso; V CONGRESO ARGENTINO DE MICROBIOLOGIA GENERAL SAMIGE; 2008

SAMIGE

Copper is an essential trace element employed in all domainsof life, but its intracellular levels must be carefully handled toprevent the formation of reactive oxygen species through afenton-like reaction. In Gram-negative bacteria copperresistance is primarily handle by the cue regulon. InEscherichia coli the cue regulon is composed by the coppersensor/regulator CueR that, upon detecting the presence ofcopper ions in the bacterial cytoplasm induces the expressionof two target genes, copA and cueO. copA codes for an integralinner-membrane copper-transporting P-type ATPase, whichensures removal of excess Cu(I) from the cytoplasm. cueOcodes for a periplasmic multi-copper oxidase responsible forthe control of copper levels through an oxygen dependentcuprous oxidase activity in aerobic conditions. Under anaerobicconditions E. coli also relies on a second system to increasecopper resistance, composed by the CusCFBA efflux pump,which is transcriptionally controlled by the two componentsystem CusR/CusS. Salmonella harbours all the cuecomponents but lacks the cus system. Despite of this,Salmonella is much more resistance to copper in anaerobicconditions than E. coli.In this work we identified a novel, Salmonella-specific CueRregulatedgene, cueP, coding for a periplasmic protein thatincrease resistance to copper both in aerobic and anaerobicconditions. We also observed that CueP overexpression partiallyrestored resistance to copper to a cueO deleted strain. Wehypothesized that in Salmonella CueP could functionallysubstitute the E. coli cus system for copper resistance inanaerobic conditions. To test this, we replaced the entire E. colichromosomal cus locus for the wild-type copy of the SalmonellacueP, including its own promoter. The CueR-dependentexpression of cueP in this strain partially suppressed the lack ofthe cus locus for copper resistance in anaerobic conditions.Moreover, overexpression of CueP completely restoredresistance to copper in a cueR cus double mutant strain inaerobic conditions, supporting its role as a copper-resistancefactor in the bacterial periplasm.Our results highlight important differences in copper handlingbetween related bacteria, and suggest that, contrary to otherenterobacterial species, Salmonella have evolved a singlepathway to overcome copper excess both in aerobic andanaerobic conditions.