Metal sensing in Salmonella: implications for pathogenesis

Abstract

Both the essentiality and toxicity of transition metals are exploited as part of mammalian immune defenses against bacterial infection. Salmonella serovars continue to cause serious medical and veterinary problems worldwide and detecting deficiency and excess of different metal ions (such as copper, iron, zinc, manganese, nickel, and cobalt) is fundamental to their virulence. This involves multiple DNA-binding metal-responsive transcription factors that discriminate between elements and trigger expression of genes that mediate appropriate responses to metal fluxes. This review focuses on the metal stresses encountered by Salmonella during infection and the roles of the different metal-sensing regulatory proteins and their target genes in adapting to these changing metal levels. Current knowledge regarding the mechanisms of metal-regulated gene expression and the structural features of sensory metal binding sites are described. In addition, the principles governing the ability of the different sensors to detect specific metals within a cell to control cytosolic metal levels are also discussed. These proteins represent potential targets for the development of new therapeutic approaches.