Salmonella pathogenicity island 2 expression negatively controlled by EIIANtr-SsrB interaction is required for Salmonella virulence.
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.
Department of Food and Animal Biotechnology, Center for Agricultural Biomaterials, and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Korea.
Jeongjoon
J
Choi
Dongwoo
D
Shin
Hyunjin
H
Yoon
Jiae
J
Kim
Chang-Ro
CR
Lee
Minjeong
M
Kim
Yeong-Jae
YJ
Seok
Sangryeol
S
Ryu
D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D044404:Genomic Islands / Q000235:genetics / Q000502:physiology*; D051379:Mice; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000254:growth & development / Q000472:pathogenicity*; D020349:Surface Plasmon Resonance; D014157:Transcription Factors / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; C119761:SsrB protein, Salmonella typhimurium; D014157:Transcription Factors; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System