The ins and outs in the evolution of copper homeostasis in Salmonella: a delicate balance between resistance and virulence

SONCINI, F. C.

Sorrento

Congreso; 11th International Copper Meeting: Bridging Clinical and Fundamental Research in Copper Biology; 2018

Salmonellosis is among the most common foodborne diseases, with millions of human infections occurring worldwide every year. The ability of Salmonella to persist and proliferate both in contaminated food and water and within host?s tissues reflects the versatility of its genetic repertoire that allows adaption to diverse and challenging environmental conditions. This also involves the participation of regulatory systems that perceive specific host?s signals and respond to them by modulating the expression of factors essential for virulence. In particular, it has been shown that this pathogen detects copper inside the Salmonella-containing vacuole in infected cells. In consequence, mutants affected in copper-resistance have reduced survival in macrophages. Most known bacterial cuproproteins localize to the envelope, which makes this compartment the main target for copper homeostasis. While in most enteric species periplasmic copper homeostasis is maintained by the CusR/CusS-controlled CusCFBA efflux system that removes surplus cellular Cu ions, this sensory and efflux system coding locus was lost in the core genome of most Salmonella subspecies. On the other hand, Salmonella acquired cueP, which codes for a periplasmic copper-chaperone. Mutants with a deletion in cueP have an increased sensitivity to copper in anaerobic conditions, and CueP can partially restore copper-resistance in the absence of oxygen in a Δcus E. coli mutant strain, suggesting that this periplasmic chaperone can substitute the CusCFBA system in the maintenance of the envelope copper homeostasis. However, it is currently unknown whether CueP can mimic Cus in the removal of the metal ion from this compartment to counteract its toxic effects. I will summarize the current knowledge about copper homeostasis in Salmonella and present our recent findings on the regulatory mechanisms that govern cueP-expression and the role of both CueP and the Cus system in Salmonella copper resistance and in intracellular survival and virulence.