A cytolysin encoded by Salmonella is required for survival within macrophages.

Libby, Stephen J.; Goebel, Werner; Ludwig, Albrecht; Buchmeier, Nancy A.; Bowe, Frances; Fang, Ferric C.; Guiney, Donald G.; Songer, J. Glenn; Heffron, Fred

doi:10.1073/pnas.91.2.489

Cited by 177 publications

(210 citation statements)

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“…The regulatory protein SlyA plays major roles in Salmonella virulence, resistance to oxidative stress and resistance to antimicrobial peptides (Buchmeier et al, 1997;Daniels et al, 1996;Kaneko et al, 2002;Libby et al, 1994;Shi et al, 2004;Watson et al, 1999). Recently, it was reported that an ssrAlacZ fusion gene in E. coli is activated in the presence of SlyA (Feng et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…The Salmonella slyA gene is implicated in virulence, survival in mouse macrophages, resistance to oxidative stress and resistance to antimicrobial peptides (Buchmeier et al, 1997;Daniels et al, 1996; Kaneko et al, 2002;Libby et al, 1994;Navarre et al, 2005;Shi et al, 2004; Watson et al, 1999). SlyA regulates the expression of a large number of genes during the stationary phase and also in the intracellular environment of host cells (Buchmeier et al, 1997;Daniels et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to these regulatory systems, it has been reported that SlyA, a virulence-associated transcriptional regulator, controls the expression of ssrAB in vivo (Feng et al, 2004;Linehan et al, 2005;Navarre et al, 2005). However, it has not yet been determined whether SlyA controls the ssrAB transcript as a direct or an indirect effect.The Salmonella slyA gene is implicated in virulence, survival in mouse macrophages, resistance to oxidative stress and resistance to antimicrobial peptides (Buchmeier et al, 1997;Daniels et al, 1996; Kaneko et al, 2002;Libby et al, 1994;Navarre et al, 2005;Shi et al, 2004; Watson et al, 1999). SlyA regulates the expression of a large number of genes during the stationary phase and also in the intracellular environment of host cells (Buchmeier et al, 1997;Daniels et al, 1996).…”

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Identification of amino acid residues of Salmonella SlyA that are critical for transcriptional regulation

Okada

Takeda‐Shitaka

et al. 2007

Microbiology

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The type III secretion system encoded by Salmonella pathogenicity island 2 (SPI-2) is essential for the intracellular survival and replication of Salmonella enterica. The expression of SPI-2 genes is dependent on a two-component regulatory system, SsrA (SpiR)/SsrB, encoded in the SPI-2 region. This paper shows that SlyA regulates transcription of the sensor kinase SsrA by binding to the ssrA promoter, indicating that SlyA is directly involved in the regulation of SPI-2 gene expression. A structure model of the SlyA dimer in complex with DNA was constructed. The model of SlyA indicated that its structure is very similar to that of other MarR family proteins. Based on this model, site-directed mutagenesis of residues located in the winged-helix region required for DNA binding and in the a-helices of the N-terminal and C-terminal regions required for dimerization of the SlyA protein was performed to identify the residues that are critical for SlyA function. Nine mutants of SlyA with single substitutions were unable to activate ssrA transcription in vivo. These mutant SlyA proteins revealed that the residues Leu-63, Val-64, Arg-65, Leu-67, Leu-70, Arg-86 and Lys-88 within the winged-helix region are required for DNA binding, and residues Leu-12 and Leu-126 within the a-helices of the N-terminal and C-terminal regions are required for efficient dimer formation. A Salmonella slyA mutant strain carrying a plasmid expressing SlyA derivatives containing mutations at these amino acid positions did not exhibit restored SlyA function in infected HeLa cells, thereby confirming the structural and functional relationships of the SlyA protein. INTRODUCTIONSalmonella enterica, a facultative intracellular pathogen, can replicate within macrophages. The intracellular survival of S. enterica serovar Typhimurium requires a number of virulence-associated proteins encoded in Salmonella pathogenicity island 2 (SPI-2) on the bacterial chromosome (Cirillo et al., 1998;Hensel, 2000;Ochman et al., 1996;Shea et al., 1996). SPI-2 encodes a two-component regulatory system, structural components of a type III secretion system (TTSS), effector proteins and chaperones, which mediate the secretion of the effectors (Cirillo et al., 1998;Hensel et al., 1998;Ochman et al., 1996;Shea et al., 1996). In infected macrophages, Salmonella replicates within a membranebound compartment (Salmonella-containing vacuole, SCV) inside the host cells (Steele-Mortimer et al., 2002). Intracellular activation of SPI-2 function is essential for SCV maturation along the phagolysosomal fusion pathway, which is responsible for the inhibition of bacterial degradation in phagolysosomes. The SPI-2 TTSS functions to export effector proteins across the SCV membrane and into the cytosol of host cells, resulting in the prevention of the recruitment of NADPH oxidase to the SCV (Gallois et al., 2001;Vazquez-Torres et al., 2000), as well as leading to the rearrangement of cellular microfilaments (Meresse et al., 2001;Miao et al., 2002) and microtubule networks (Brumell et al., 20...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of amino acid residues of Salmonella SlyA that are critical for transcriptional regulation

Okada

Takeda‐Shitaka

et al. 2007

Microbiology

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“…For example, susceptibility of mice to salmonellosis correlates with net growth of S. typhimurium within isolated macrophages (reviewed by Dunlap et al, 1994) and Salmonella mutants that are unable to survive in murine macrophages have reduced virulence in mice (Fields et al, 1986 ;Libby et al, 1994 ;Hensel et al, 1998). However, several independent groups have recently reported that Salmonella is highly cytolytic for macrophages (Guilloteau et al, 1996 ;Chen et al, 1996 ;Lindgren et al, 1996), suggesting that the contribution of macrophage infection to pathogenesis is more complex than previously believed.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Salmonella serotypes with porcine macrophages in vitro does not correlate with virulence

et al. 2000

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The interaction between Salmonella serotypes and macrophages is potentially instrumental in determining the outcome of infection. The nature of this interaction was characterized with respect to virulence and serotype-host specificity using pigs as the infection model. Experimental infection with Salmonella typhimurium , Salmonella choleraesuis or Salmonella dublin resulted in enteric, systemic or asymptomatic infection, respectively, which correlates well with the association of S. choleraesuis with systemic disease in pigs in epidemiological studies. Persistence within porcine alveolar macrophages in vitro did not directly correlate with virulence since S. typhimurium persisted in the highest numbers, and S. choleraesuis in the lowest. Comparison to other studies revealed that the relatively high persistence of S. typhimurium in macrophages correlates with its virulence in a broad range of animals : this could be a virulence mechanism for broad-hostrange serotypes. There were little or no significant differences in the induction of pro-inflammatory cytokines by macrophages infected with the three serotypes. S. typhimurium and S. dublin, but not S. choleraesuis, damaged porcine macrophages, and the mechanism of damage did not resemble apoptosis. In conclusion, the virulence of Salmonella serotypes in pigs did not directly correlate with their interaction with porcine macrophages in vitro. The interaction of Salmonella and macrophages in vitro may not accurately model their interaction in vivo, and this will form the basis of further study.

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“…The members of the SlyA regulon encode secreted, membrane-associated and periplasmic proteins, leading to the suggestion that a major role of SlyA involves controlling the composition of the bacterial cell envelope (Navarre et al, 2005;Spory et al, 2002;Stapleton et al, 2002). SlyA also contributes to Salmonella virulence and is important in resisting the oxidative stress and antimicrobial peptides that are encountered in macrophages (Libby et al, 1994;Stapleton et al, 2002).…”

Section: H-ns Antagonism By Slya-like Proteinsmentioning

confidence: 99%

Anti-silencing: overcoming H-NS-mediated repression of transcription in Gram-negative enteric bacteria

2008

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A cytolysin encoded by Salmonella is required for survival within macrophages.

Cited by 177 publications

References 30 publications

Identification of amino acid residues of Salmonella SlyA that are critical for transcriptional regulation

Identification of amino acid residues of Salmonella SlyA that are critical for transcriptional regulation

Interaction of Salmonella serotypes with porcine macrophages in vitro does not correlate with virulence

Anti-silencing: overcoming H-NS-mediated repression of transcription in Gram-negative enteric bacteria

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