THE Salmonella enterica MAGNESIUM STIMULON

M.E. CASTELLI, M.L. CABEZA, F. C. SONCINI AND E. GARCÍA VÉSCOVI

San Pablo, Brasil

Conferencia; II Sao Paulo Research Conferences, Mechanisms of infection and vaccines.; 2004

Universidad de San Pablo

In the pathogenic bacterium Salmonella enterica, magnesium plays a fundamental role during the infection process. Salmonella utilizes the level of environmental Mg2+ as a signal to control the expression of several essential virulence determinants. We have identified that this sensing process is mediated by a specific signal-transduction system known as PhoP/PhoQ. Extracellular Mg2+ controls a specific response-regulator phosphatase activity in the membrane-associated sensor PhoQ, inactivating the transcriptional regulator PhoP. We addressed the characterization of the interaction between the two component partners to determine the molecular basis for the fidelity in their recognition. Our results reveal that DHp is the PhoQ domain that concentrates structural and functional determinants that are key to homodimerization, to specific PhoP recognition and to the signal-induced phosphate exchange activities. Besides, phosphorylation of the response regulator promotes its self-association, allowing the protein to recognize and interact with a direct-repeat sequence located in the promoter region of a set of PhoP-activated genes (pags). On the other hand, pags that do not harbor the PhoP-box at their promoter regions are indirectly controlled by this system. We are currently investigating putative intermediaries in their Mg2+-controlled regulation. Interestingly, most of these indirectly-regulated genes are Salmonella-specific and were probably acquired by horizontal transfer. Recently, we have uncovered a novel Mg2+ regulatory system that constitutes a novel transduction cascade with PhoP/PhoQ. The analysis of this system is relevant to understand how extracellular Mg2+ coordinates with other environmental signals to guarantee the proper function of vital intracellular mechanisms.