Limits...
The Role of the spv Genes in Salmonella Pathogenesis.

Guiney DG, Fierer J - Front Microbiol (2011)

Bottom Line: The exact mechanisms by which SpvB and SpvC act in concert to enhance virulence are still unclear.SpvB exhibits a cytotoxic effect on host cells and is required for delayed cell death by apoptosis following intracellular infection.Strains isolated from systemic infections of immune compromised patients, particularly HIV patients, usually carry the spv locus, strongly suggesting that CD4 T cells are required to control disease due to Salmonella that are spv positive.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Diego School of Medicine La Jolla, CA, USA.

ABSTRACT
Salmonella strains cause three main types of diseases in people: gastroenteritis, enteric (typhoid) fever, and non-typhoid extra-intestinal disease with bacteremia. Genetic analysis indicates that each clinical syndrome requires distinct sets of virulence genes, and Salmonella isolates differ in their constellation of virulence traits. The spv locus is strongly associated with strains that cause non-typhoid bacteremia, but are not present in typhoid strains. The spv region contains three genes required for the virulence phenotype in mice: the positive transcriptional regulator spvR and two structural genes spvB and spvC. SpvB and SpvC are translocated into the host cell by the Salmonella pathogenicity island-2 type-three secretion system. SpvB prevents actin polymerization by ADP-ribosylation of actin monomers, while SpvC has phosphothreonine lyase activity and has been shown to inhibit MAP kinase signaling. The exact mechanisms by which SpvB and SpvC act in concert to enhance virulence are still unclear. SpvB exhibits a cytotoxic effect on host cells and is required for delayed cell death by apoptosis following intracellular infection. Strains isolated from systemic infections of immune compromised patients, particularly HIV patients, usually carry the spv locus, strongly suggesting that CD4 T cells are required to control disease due to Salmonella that are spv positive. This association is not seen with typhoid fever, indicating that the pathogenesis and immunology of typhoid have fundamental differences from the syndrome of non-typhoid bacteremia.

No MeSH data available.


Related in: MedlinePlus

Map of the spv region found on virulence plasmids in subspecies 1 strains, not drawn to scale. The spvR gene is transcribed separately from the spvABCD genes. SpvR activates transcription at both promoters in concert with the RpoS sigma factor. The expansion shows the general structure of the SpvB protein, with N- and C-terminal domains separated by a run of proline residues (P). EAE denotes residues at the active site for the ADP-ribosylation activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3117207&req=5

Figure 1: Map of the spv region found on virulence plasmids in subspecies 1 strains, not drawn to scale. The spvR gene is transcribed separately from the spvABCD genes. SpvR activates transcription at both promoters in concert with the RpoS sigma factor. The expansion shows the general structure of the SpvB protein, with N- and C-terminal domains separated by a run of proline residues (P). EAE denotes residues at the active site for the ADP-ribosylation activity.

Mentions: Non-typhoid Salmonella strains associated with extra-intestinal infections in humans and animals carry an additional locus termed spv (Guiney et al., 1994, 1995; Fierer and Guiney, 2001). The spv genes are located within a highly homologous region contained on virulence plasmids found in the subspecies 1 lineage of S. enterica, and were named for the designation Salmonella plasmid virulence (Figure 1). The spv locus enhances mouse virulence by several orders of magnitude in LD50, depending on the Salmonella serovar and the mouse strain. The virulence phenotype is seen in both ItyS and ItyR mice, also referred to as Nramp1 (Slc11a1) mutant and wild-type mice respectively. Furthermore the spv effect has also been documented experimentally in calves and pigs and by molecular epidemiology in humans (Fierer et al., 1992; Libby et al., 1997). Subsequent work showed that the spv genes are located in the chromosome in certain other S. enterica lineages (Boyd and Hartl, 1998; Libby et al., 2002). spv-carrying serovars associated with human disease include Typhimurium, Enteritidis, Choleraesuis, Dublin, and Arizona. Certain host-adapted animal pathogens, such as Gallinarum/Pullorum and Abortusovis, also contain the spv locus. The plasmid spvABCD genes are arranged in an operon positively regulated by the upstream spvR gene, as shown in Figure 1 (Fang et al., 1991; Krause et al., 1991, 1992). The spvD gene is missing in the chromosomal locus as found in serovar Arizona (Libby et al., 2002). The SpvR protein is a positive transcriptional regulator of the LysR family and binds to inverted repeat recognition sequences upstream of its own promoter and the spvA promoter (Krause et al., 1991, 1995; Grob and Guiney, 1996; Grob et al., 1997). Transcription initiation at both promoters requires the alternative sigma factor RpoS (“stationary phase sigma factor”; Fang et al., 1992; Chen et al., 1995). Expression of the spv operon is induced by the intracellular environment of host cells and is dependent on both SpvR and RpoS (Fierer et al., 1993; Chen et al., 1996). Genetic analysis demonstrates that the spvR and spvBC genes are required for the virulence phenotype of the spv locus, while mutations in spvA and spvD do not have a reproducible virulence phenotype in mice (Roudier et al., 1992).


The Role of the spv Genes in Salmonella Pathogenesis.

Guiney DG, Fierer J - Front Microbiol (2011)

Map of the spv region found on virulence plasmids in subspecies 1 strains, not drawn to scale. The spvR gene is transcribed separately from the spvABCD genes. SpvR activates transcription at both promoters in concert with the RpoS sigma factor. The expansion shows the general structure of the SpvB protein, with N- and C-terminal domains separated by a run of proline residues (P). EAE denotes residues at the active site for the ADP-ribosylation activity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117207&req=5

Figure 1: Map of the spv region found on virulence plasmids in subspecies 1 strains, not drawn to scale. The spvR gene is transcribed separately from the spvABCD genes. SpvR activates transcription at both promoters in concert with the RpoS sigma factor. The expansion shows the general structure of the SpvB protein, with N- and C-terminal domains separated by a run of proline residues (P). EAE denotes residues at the active site for the ADP-ribosylation activity.
Mentions: Non-typhoid Salmonella strains associated with extra-intestinal infections in humans and animals carry an additional locus termed spv (Guiney et al., 1994, 1995; Fierer and Guiney, 2001). The spv genes are located within a highly homologous region contained on virulence plasmids found in the subspecies 1 lineage of S. enterica, and were named for the designation Salmonella plasmid virulence (Figure 1). The spv locus enhances mouse virulence by several orders of magnitude in LD50, depending on the Salmonella serovar and the mouse strain. The virulence phenotype is seen in both ItyS and ItyR mice, also referred to as Nramp1 (Slc11a1) mutant and wild-type mice respectively. Furthermore the spv effect has also been documented experimentally in calves and pigs and by molecular epidemiology in humans (Fierer et al., 1992; Libby et al., 1997). Subsequent work showed that the spv genes are located in the chromosome in certain other S. enterica lineages (Boyd and Hartl, 1998; Libby et al., 2002). spv-carrying serovars associated with human disease include Typhimurium, Enteritidis, Choleraesuis, Dublin, and Arizona. Certain host-adapted animal pathogens, such as Gallinarum/Pullorum and Abortusovis, also contain the spv locus. The plasmid spvABCD genes are arranged in an operon positively regulated by the upstream spvR gene, as shown in Figure 1 (Fang et al., 1991; Krause et al., 1991, 1992). The spvD gene is missing in the chromosomal locus as found in serovar Arizona (Libby et al., 2002). The SpvR protein is a positive transcriptional regulator of the LysR family and binds to inverted repeat recognition sequences upstream of its own promoter and the spvA promoter (Krause et al., 1991, 1995; Grob and Guiney, 1996; Grob et al., 1997). Transcription initiation at both promoters requires the alternative sigma factor RpoS (“stationary phase sigma factor”; Fang et al., 1992; Chen et al., 1995). Expression of the spv operon is induced by the intracellular environment of host cells and is dependent on both SpvR and RpoS (Fierer et al., 1993; Chen et al., 1996). Genetic analysis demonstrates that the spvR and spvBC genes are required for the virulence phenotype of the spv locus, while mutations in spvA and spvD do not have a reproducible virulence phenotype in mice (Roudier et al., 1992).

Bottom Line: The exact mechanisms by which SpvB and SpvC act in concert to enhance virulence are still unclear.SpvB exhibits a cytotoxic effect on host cells and is required for delayed cell death by apoptosis following intracellular infection.Strains isolated from systemic infections of immune compromised patients, particularly HIV patients, usually carry the spv locus, strongly suggesting that CD4 T cells are required to control disease due to Salmonella that are spv positive.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of California San Diego School of Medicine La Jolla, CA, USA.

ABSTRACT
Salmonella strains cause three main types of diseases in people: gastroenteritis, enteric (typhoid) fever, and non-typhoid extra-intestinal disease with bacteremia. Genetic analysis indicates that each clinical syndrome requires distinct sets of virulence genes, and Salmonella isolates differ in their constellation of virulence traits. The spv locus is strongly associated with strains that cause non-typhoid bacteremia, but are not present in typhoid strains. The spv region contains three genes required for the virulence phenotype in mice: the positive transcriptional regulator spvR and two structural genes spvB and spvC. SpvB and SpvC are translocated into the host cell by the Salmonella pathogenicity island-2 type-three secretion system. SpvB prevents actin polymerization by ADP-ribosylation of actin monomers, while SpvC has phosphothreonine lyase activity and has been shown to inhibit MAP kinase signaling. The exact mechanisms by which SpvB and SpvC act in concert to enhance virulence are still unclear. SpvB exhibits a cytotoxic effect on host cells and is required for delayed cell death by apoptosis following intracellular infection. Strains isolated from systemic infections of immune compromised patients, particularly HIV patients, usually carry the spv locus, strongly suggesting that CD4 T cells are required to control disease due to Salmonella that are spv positive. This association is not seen with typhoid fever, indicating that the pathogenesis and immunology of typhoid have fundamental differences from the syndrome of non-typhoid bacteremia.

No MeSH data available.


Related in: MedlinePlus