“Interaction between the PhoP/PhoQ and PmrA/PmrB virulence regulatory systems in Salmonella typhimurium”

M. E. CASTELLI, S. LEJONA, E. GARCÍA VÉSCOVI Y F. C. SONCINI

Rio de Janeiro, Brasil

Congreso; 1999 Meeting of International Research Scholars, Howard Hughes Medical Institute; 1999

Howard Hughes Medical Institute,

Interaction between the PhoP/PhoQ and PmrA/PmrB virulence regulatory systems in Salmonella typhimurium María Eugenia Castelli, Sergio Lejona,  Eleonora García Véscovi y Fernando C Soncini. Departamento de Microbiología, Facultad de Ciencias Bioquímicas y Farmaceúticas, Universidad Nacional de Rosario. Suipacha 531 (2000) Rosario   Bacteria must modulate the expression of their gene repertoire to susvive in their rapidly changing environment. Two-component systems are key to this process. Such systems are usually composed of a membrane sensor/kinase protein that, upon sensing modifications in the environment, transduces the information by phosphorylation to the second component, which mediates the appropriate response to the stimuli. In Salmonella the PhoP/PhoQ system controls the adaptation to Mg deprivation by altering the requirements and the distribution of Mg within the cell, including modifications of the cation binding sites in the lipopolysacharide (LPS), mediated by the PmrA/PmrB regulatory system. These modifications result in an increased resistance to antibacterial peptides and survival inside macrophages. We investigated the interaction between the PhoP/PhoQ and PmrA/PmrB systems in order to elucidate the molecular events that take place during the Mg induction of the PmrA-regualtade genes. We determined that both sensor proteins harbor an autokinase activity and that phosphotransfer was specific to their cognate regulators. Phosphorylated PhoP was stable for several minutes, whereas PmrA became dephosphorylated rapidly. Addition of PmrB to the PhoQ/PhoP reaction mixture increased the dephosphorylation of PhoQ, indicating a direct interaction between both systems. These results are in agreement with our previous genetic data that suggested a phosphorelay cascade PhoQ-PhoP-PmrB-PmrA. This is the first described cascade composed by two independent signal-transduction systems that interact to process specific modifications in the invironment and may be considered ancestral to phosphorelays found in other bacteria, such as Bacillus subtilis (KinA/Spo0F/0B/0A) and Bordetella pertussis (BvgS/A).