Salmonella-specific genes involved in zinc homeostasis and virulence

SCAMPOLI, N. L.; CHECA, S. K.; SONCINI, F. C.

Rosario

Congreso; IX Congreso Argentino de Microbiología General, SAMIGE; 2013

Sociedad Argentina de Microbiología General, SAMIGE

Zinc is an essential ion for life. It is required for structural functions, as a biological catalyst in a large number of proteins and as a signal molecule in various cellular processes. Therefore, its acquisition is critical to ensure cell viability in both eukaryotes and prokaryotes. The serum concentration of zinc is in the micromolar range, but its availability is further restricted because it is tightly bound to serum proteins, and it has been speculated that this limitation would be a defense mechanism against bacterial infections. Indeed, in recent years, the ability to obtain this ion by pathogenic bacteria has been correlated with their ability to colonize host tissues, particularly for intracellular pathogens such as Salmonella, as mutants in znuABC, the operon coding for a Zn transporter, are highly affected for virulence. Expression of this operon is controlled by Zur, an ancestral enterobacterial Zn regulator. To better understand the mechanisms used by this pathogen to maintain a proper quota of this essential ion we searched for other genes controlled by Zur in Salmonella. Among the loci identified in our screening we focused on two new, highly similar and species-specific genes. We confirmed that the expression of both genes is modulated by Zn in a Zur-dependent manner. Furthermore, mutants in these genes showed a defect in macrophage survival, indicating that their products are required for full virulence of this pathogen. Our results are key in the understanding of the actions taken by Salmonella to control gene expression in order to prosper within the infected host.