The SsrAB Virulon of Salmonella enterica

Sandra Billig; Alfonso Felipe-López; Michael Hensel

doi:10.1128/9781555818524.ch20

Chapter 20 : The SsrAB Virulon of Salmonella enterica

Authors: Sandra Billig¹, Alfonso Felipe-López¹, Michael Hensel¹

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Affiliations: 1: Abteilung Mikrobiologie, Universität Osnabrück, Osnabrück, Germany

Content Type: Monograph

Publication Year: 2013

Category: Bacterial Pathogenesis

Book DOI: 10.1128/9781555818524

Chapter DOI: 10.1128/9781555818524.ch20

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Abstract:

This chapter focuses on the function of the regulatory system SsrAB of Salmonella enterica, which controls expression of virulence factors for the intracellular phase of the life of the pathogen. It discusses the experimental data and current understanding of the function of the two-component system SsrAB. SsrAB is encoded by genes in Salmonella pathogenicity islands 2 (SPI2) and is necessary to control expression of virulence genes during the intracellular stage of Salmonella infection. Intracellular survival and replication is dependent on the function of the SPI2-encoded T3SS (SPI2-T3SS). The signature-tagged mutagenesis screen initially identified various transposon-insertion mutants with highly reduced virulence in the murine model of systemic infection. A comparative analysis of expression levels under in vitro conditions indicated high diversity in expression levels of the various genes encoding structural components and effector proteins of the SPI2-T3SS. In contrast to the case with SsrA, several experimental approaches have been made towards understanding the function of SsrB, the response regulator of the SsrAB two-component system. The ancestral OmpR/EnvZ two-component system regulates the porin genes ompF and ompC in response to changes in osmolarity. The SPI1-encoded HilD regulatory protein, which activates the expression of SPI1 genes, has been suggested to control the switch from SPI1 to SPI2 induction. The levels of regulation range from the SPI2-encoded regulatory system SsrAB and core genome-encoded regulators to global control elements such as DNA topology regulators.

Citation: Billig S, Felipe-López A, Hensel M. 2013. The SsrAB Virulon of Salmonella enterica, p 386-401. In Vasil M, Darwin A (ed), Regulation of Bacterial Virulence. ASM Press, Washington, DC. doi: 10.1128/9781555818524.ch20

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The SsrAB Virulon of Salmonella enterica

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Figure 1

The SsrAB virulon in Salmonella enterica. (A) Intracellular salmonellae reside within the SCV, a membrane-bound compartment considered growth restricting due to nutritional limitations. By means of the SPI2-T3SS, intracellular salmonellae modify host cell functions, resulting in intracellular proliferation. (B) Unknown signals present in the SCV act on the SsrA sensor and, in turn, result in activation of the SsrAB virulon. (C) SsrB activates the transcription of several operons within SPI2 encoding the SPI2-T3SS, cognate effector proteins, and the SsrAB regulatory system, various loci outside of SPI2 encoding effector proteins of the SPI2-T3SS, and further loci with unknown contribution to the intracellular lifestyle. doi:10.1128/9781555818524.ch20f1

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Figure 1

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Figure 2

Models for the domain organization of SsrA and SsrB. The predicted domain organization of SsrA (A) and SsrB (B) and positions of domains and functional residues are depicted. (C) Model for the topology of SsrA and SsrB. Red circle, unknown signal received by SsrA; green circle with P, phosphate group. CM, cytoplasmic membrane. doi:10.1128/9781555818524.ch20f2

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Figure 2

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Figure 3

Binding specificity of SsrB and regulation of ssrAB expression. (A) The palindromic consensus motif of promoters of the SsrAB virulon as identified by one-hybrid screens and ChIP-on-chip experiments (modified from Tomljenovic-Berube et al., 2010 ). (B) The gene arrangement of ssrAB in SPI2 is depicted. The yellow box (A1) indicates the binding site location of OmpR (low affinity) and OmpR-P (high affinity) upstream of the transcriptional start site of ssrA. The light blue boxes (A2 to A5) indicate additional OmpR-P binding sites. Boxes B1 to B3 indicate the OmpR-P binding sites in the ssrB region. Overlapping binding sites for the C-terminal domain of SsrB are shown as red boxes ( Feng et al., 2004 ). The transcriptional start sites of ssrA and ssrB are indicated by arrows and labeled +1, while the translational start sites are denoted by green arrows for ssrA and ssrB. The labels +164 and +150 indicate the presence of 164- and 150-nucleotide UTR in the ssrA and ssrB transcripts, respectively ( Feng et al., 2003 ). doi:10.1128/9781555818524.ch20f3

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Figure 3

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Figure 4

Model for regulatory circuits of the SsrAB virulon (modified from Fass and Groisman, 2009 ). The two-component systems (green boxes) SsrAB, EnvZ/OmpR, and PhoPQ are involved in SPI2 regulation. OmpR activates SPI2 genes by binding to the promoter and inducing the expression of ssrA and ssrB. PhoP directly binds the ssrB promoter and thereby indirectly induces ssrA transcription. SsrB binds to all SPI2 promoters, including ssrA and its own promoter, for which it is required for antagonizing the repression activity of H-NS. Transcription factors (red boxes) further affect the SsrAB regulon, with SlyA affecting ssrAB expression and EIIANtr directly interacting with SsrB at the posttranscriptional level, thereby preventing SsrB-induced gene expression. The expression of slyA is controlled by PhoP. The SPI1-encoded HilD transcription factor is also involved (under certain conditions) in antagonizing H-NS activity. The NAPs (orange boxes) H-NS, Hha, and YdgT function as general negative SPI2 regulators, while Fis and IHF are NAPs that have a positive effect on SPI2 as well as SPI1 gene expression ( Wilson et al., 2007 ; Fass and Groisman, 2009 ). doi:10.1128/9781555818524.ch20f4

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