Salmonella pathogenicity island 2 expression negatively controlled by EIIA ^Ntr –SsrB interaction is required for Salmonella virulence

Abstract

SsrA/SsrB is a primary two-component system that mediates the survival and replication of Salmonella within host cells. When activated, the SsrB response regulator directly promotes the transcription of multiple genes within Salmonella pathogenicity island 2 (SPI-2). As expression of the SsrB protein is promoted by several transcription factors, including SsrB itself, the expression of SPI-2 genes can increase to undesirable levels under activating conditions. Here, we report that Salmonella can avoid the hyperactivation of SPI-2 genes by using ptsN-encoded EIIA Ntr , a component of the nitrogen-metabolic phosphotransferase system. Under SPI-2-inducing conditions, the levels of SsrB-regulated gene transcription increased abnormally in a ptsN deletion mutant, whereas they decreased in a strain overexpressing EIIA Ntr . We found that EIIA Ntr controls SPI-2 genes by acting on the SsrB protein at the posttranscriptional level. EIIA Ntr interacted directly with SsrB, which prevented the SsrB protein from binding to its target promoter. Finally, the Salmonella strain, either lacking the ptsN gene or overexpressing EIIA Ntr , was unable to replicate within macrophages, and the ptsN deletion mutant was attenuated for virulence in mice. These results indicated that normal SPI-2 gene expression maintained by an EIIA Ntr -SsrB interaction is another determinant of Salmonella virulence.virulence gene regulation | nitrogen-metabolic phosphotransferase system (PTS) | protein-protein interaction

The Bacterial Phosphoenolpyruvate:Carbohydrate Phosphotransferase System: Regulation by Protein Phosphorylation and Phosphorylation-Dependent Protein-Protein Interactions

“…Second, deletion of EIIA Ntr was found to indirectly affect the virulence of this pathogen. EIIA Ntr was reported to interact with the response regulator SsrB, which is required for the expression of numerous genes located within pathogenicity island 2 of this bacterium (131). The interaction with EIIA Ntr prevents SsrB from stimulating the expression of the genes in pathogenicity island 2.…”

Nitrogen Assimilation in Escherichia coli: Putting Molecular Data into a Systems Perspective

“…Third, EIIA Ntr has also been shown to be a member of the E regulon and to play a role in maintaining cell envelope integrity upon stress (444). Fourth, for Salmonella, EIIA Ntr has been demonstrated to interact directly with SsrB, the response regulator of the SsrA/SsrB two-component system that mediates survival and replication within host cells (445).…”

The influence of the accessory genome on bacterial pathogen evolution

“…17 Plant and animal pathogens can be disseminated into the environment, which can potentially have an important influence on pathogen evolution (see also Morris et al). 109 For example, pathogens may be exposed to a variety of bacteriophages [e.g., vibriophages], 52 and they frequently encounter other organisms that may act as alternative hosts and have resident microbial populations. 110 Moreover, several virulence genes in human pathogens have been experimentally determined to provide resistance to grazing protozoa 111,112 or to kill amoeba associated with them in biofilms.…”

“…It was found that this PAI has integrated into the host regulatory network and is expressed only at the critical times of infection, but switched off at other times to avoid toxicity or energy burdens. 52 Investigations into GIs are helping to unravel host range restriction in a number of pathogens. Salmonella enterica Gallinarum is a pathogen with a host range specific to poultry, while S. enterica Enteritidis is a broad host range pathogen that is a leading cause of gastrointestinal salmonellosis in humans and many other species, but only colonizes poultry sub-clinically (i.e., is asymptomatic).…”