Salmonella pathogenicity island 2 expression negatively controlled by EIIANtr-SsrB interaction is required for Salmonella virulence

摘要

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 hyperactiva-tion of SPI-2 genes by using ptsN-encoded EIIANtr, 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 EIIANtr. We found that EIIANtr controls SPI-2 genes by acting on the SsrB protein at the posttran-scriptional level. EIIANtr 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 over-expressing EIIANtr, 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 EIIANtr-SsrB interaction is another determinant of Salmonella virulence.