Two-Component Regulators ControlhilAExpression by ControllingfimZandhilEExpression within Salmonella enterica Serovar Typhimurium

Abstract

Salmonellae initiate disease through the invasion of host cells within the intestine. This ability to invade requires the coordinated action of numerous genes, many of which are found withinSalmonellapathogenicity island 1 (SPI-1). The key to this process is the ability of the bacteria to respond to the environment, thereby upregulating the necessary genes under optimal conditions. Central to the control of SPI-1 is the transcriptional activatorhilA. Work has identified at least 10 different activators and 8 different repressors responsible for the control ofhilA. We have previously shown thathilEis aSalmonella-specific negative regulator that is able to represshilAexpression and invasion. Additionally,fimZ, a transcriptional activator responsible for the expression of type I fimbriae as well as flagellar genes, has also been implicated in this process.fimZis homologous to response regulators from other two-component regulatory systems, although a sensor for the system has not been identified. ThephoPQandphoBRregulons are both two-component systems that negatively affecthilAexpression, although the mechanism of action has not been determined. Our results show that PhoBR is capable of inducingfimZexpression, whereas PhoPQ does not affectfimZexpression but does upregulatehilEin an FimZ-dependent manner. Therefore, phosphate (sensed by PhoBR) and magnesium (sensed by PhoPQ) levels are important in controllinghilAexpression levels whenSalmonellais in the intestinal environment.