scholarly journals Cystathionine β-Lyase Is Important for Virulence of Salmonella enterica Serovar Typhimurium

2004 ◽  
Vol 72 (6) ◽  
pp. 3310-3314 ◽  
Author(s):  
Linda J. Ejim ◽  
Vanessa M. D'Costa ◽  
Nadine H. Elowe ◽  
J. Concepción Loredo-Osti ◽  
Danielle Malo ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Antibacterial Agents ◽  
Antimicrobial Agents ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Bacterial Virulence ◽  
Methionine Biosynthesis ◽  
Insertional Inactivation ◽  
Serovar Typhimurium

ABSTRACT The biosynthesis of methionine in bacteria requires the mobilization of sulfur from Cys by the formation and degradation of cystathionine. Cystathionine β-lyase, encoded by metC in bacteria and STR3 in Schizosaccharomyces pombe, catalyzes the breakdown of cystathionine to homocysteine, the penultimate step in methionine biosynthesis. This enzyme has been suggested to be the target for pyridinamine antimicrobial agents. We have demonstrated, by using purified enzymes from bacteria and yeast, that cystathionine β-lyase is not the likely target of these agents. Nonetheless, an insertional inactivation of metC in Salmonella enterica serovar Typhimurium resulted in the attenuation of virulence in a mouse model of systemic infection. This result confirms a previous chemical validation of the Met biosynthetic pathway as a target for the development of antibacterial agents and demonstrates that cystathionine β-lyase is important for bacterial virulence.

scholarly journals Virulence Plasmid-Borne spvB and spvC Genes Can Replace the 90-Kilobase Plasmid in Conferring Virulence to Salmonella enterica Serovar Typhimurium in Subcutaneously Inoculated Mice

2001 ◽  
Vol 183 (15) ◽  
pp. 4652-4658 ◽  
Author(s):  
Hidenori Matsui ◽  
Christopher M. Bacot ◽  
Wendy A. Garlington ◽  
Thomas J. Doyle ◽  
Steve Roberts ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Reticuloendothelial System ◽  
Host Cells ◽  
Virulence Plasmid ◽  
Replication Rate ◽  
Oral Inoculation ◽  
Low Copy Number ◽  
Serovar Typhimurium

ABSTRACT In a mouse model of systemic infection, the spv genes carried on the Salmonella enterica serovar Typhimurium virulence plasmid increase the replication rate of salmonellae in host cells of the reticuloendothelial system, most likely within macrophages. A nonpolar deletion in the spvB gene greatly decreased virulence but could not be complemented by spvBalone. However, a low-copy-number plasmid expressing spvBCfrom a constitutive lacUV5 promoter did complement thespvB deletion. By examining a series of spvmutations and cloned spv sequences, we deduced thatspvB and spvC could be sufficient to confer plasmid-mediated virulence to S. enterica serovar Typhimurium. The spvBC-bearing plasmid was capable of replacing all of the spv genes, as well as the entire virulence plasmid, of serovar Typhimurium for causing systemic infection in BALB/c mice after subcutaneous, but not oral, inoculation. A point mutation in the spvBC plasmid preventing translation but not transcription of spvC eliminated the ability of the plasmid to confer virulence. Therefore, it appears that both spvB and spvC encode the principal effector factors for Spv- and plasmid-mediated virulence of serovar Typhimurium.

scholarly journals Salmonella enterica Serovars Typhi and Paratyphi A are avirulent in newborn and infant mice even when expressing virulence plasmid genes of Salmonella Typhimurium

2010 ◽  
Vol 4 (11) ◽  
pp. 723-731 ◽  
Author(s):  
Javier Santander ◽  
Roy Curtiss III
Keyword(s):  
Salmonella Enterica ◽  
Virulence Genes ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Virulence Plasmid ◽  
Susceptible Animal ◽  
Human Host ◽  
Adult Mice ◽  
Serovar Typhimurium ◽  
Plasmid Genes

Background: Salmonella enterica serovars Typhi and Paratyphi A are human host-restricted pathogens. Therefore, there is no small susceptible animal host that can be used to assess the virulence and safety of vaccine strains derived from these Salmonella serovars.  However, infant mice have been used to evaluate virulence and colonization by another human host-restricted pathogen, Vibrio cholerae.  Methodology: The possibility that infant mice host could be adapted for Salmonella led us to investigate the susceptibility of newborn and infant mice to oral infection with S. Typhi and S. Paratyphi A. Salmonella enterica serovar Typhimurium causes enteric fever in adult mice and this system has been used as a model for human typhoid. The pSTV virulence plasmid, not present in S. Typhi and S. Paratyphi A, plays an essential role in S. Typhimurium colonization and systemic infection of mice. We also conjugated pSTV into S. Typhi and S. Paratyphi A serovars and evaluated these transconjugants in newborn and infant mice.  Results: We determined that the spv virulence genes from the S. Typhimurium virulence plasmid are expressed in S. Typhi and S. Paratyphi A in a RpoS dependent fashion. Also, we determined that S. Typhi and S. Paratyphi A with and without pSTV transiently colonize newborn and infant mice tissues. Conclusion: Newborn and infant mice infected with S. Typhi and S. Paratyphi A do not succumb to the infection and that carriage of the S. Typhimurium virulence plasmid, pSTV, did not influence these results.

scholarly journals Identification of GtgE, a Novel Virulence Factor Encoded on the Gifsy-2 Bacteriophage of Salmonella enterica Serovar Typhimurium

2002 ◽  
Vol 184 (19) ◽  
pp. 5234-5239 ◽  
Author(s):  
Theresa D. Ho ◽  
Nara Figueroa-Bossi ◽  
Minhua Wang ◽  
Sergio Uzzau ◽  
Lionello Bossi ◽  
...  
Keyword(s):  
Virulence Factor ◽  
Salmonella Enterica ◽  
Virulence Genes ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Open Reading Frames ◽  
Effector Protein ◽  
Protein Sequence Analysis ◽  
Serovar Typhimurium ◽  
Reading Frames

ABSTRACT The Gifsy-2 temperate bacteriophage of Salmonella enterica serovar Typhimurium contributes significantly to the pathogenicity of strains that carry it as a prophage. Previous studies have shown that Gifsy-2 encodes SodCI, a periplasmic Cu/Zn superoxide dismutase, and at least one additional virulence factor. Gifsy-2 encodes a Salmonella pathogenicity island 2 type III secreted effector protein. Sequence analysis of the Gifsy-2 genome also identifies several open reading frames with homology to those of known virulence genes. However, we found that null mutations in these genes did not individually have a significant effect on the ability of S. enterica serovar Typhimurium to establish a systemic infection in mice. Using deletion analysis, we have identified a gene, gtgE, which is necessary for the full virulence of S. enterica serovar Typhimurium Gifsy-2 lysogens. Together, GtgE and SodCI account for the contribution of Gifsy-2 to S. enterica serovar Typhimurium virulence in the murine model.

scholarly journals Identification and Functional Characterization of Chicken Toll-Like Receptor 5 Reveals a Fundamental Role in the Biology of Infection with Salmonella enterica Serovar Typhimurium

2005 ◽  
Vol 73 (4) ◽  
pp. 2344-2350 ◽  
Author(s):  
Muhammad Iqbal ◽  
Victoria J. Philbin ◽  
G. S. K. Withanage ◽  
Paul Wigley ◽  
Richard K. Beal ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Functional Characterization ◽  
Systemic Infection ◽  
Structural Similarity ◽  
Conserved Sequence ◽  
Receptor Repertoire ◽  
Serovar Typhimurium ◽  
Toll Like Receptor 5

ABSTRACT Toll-like receptors (TLRs) are a major component of the pattern recognition receptor repertoire that detect invading microorganisms and direct the vertebrate immune system to eliminate infection. In chickens, the differential biology of Salmonella serovars (systemic versus gut-restricted localization) correlates with the presence or absence of flagella, a known TLR5 agonist. Chicken TLR5 (chTLR5) exhibits conserved sequence and structural similarity with mammalian TLR5 and is expressed in tissues and cell populations of immunological and stromal origin. Exposure of chTLR5+ cells to flagellin induced elevated levels of chicken interleukin-1β (chIL-1β) but little upregulation of chIL-6 mRNA. Consistent with the flagellin-TLR5 hypothesis, an aflagellar Salmonella enterica serovar Typhimurium fliM mutant exhibited an enhanced ability to establish systemic infection. During the early stages of infection, the fliM mutant induced less IL-1β mRNA and polymorphonuclear cell infiltration of the gut. Collectively, the data represent the identification and functional characterization of a nonmammalian TLR5 and indicate a role in restricting the entry of flagellated Salmonella into systemic sites of the chicken.

scholarly journals Reduced Flux through the Purine Biosynthetic Pathway Results in an Increased Requirement for Coenzyme A in Thiamine Synthesis in Salmonella enterica Serovar Typhimurium

2000 ◽  
Vol 182 (1) ◽  
pp. 236-240 ◽  
Author(s):  
Michael Frodyma ◽  
Aileen Rubio ◽  
D. M. Downs
Keyword(s):  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Coenzyme A ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Thiamine Pyrophosphate ◽  
Nutritional Requirement ◽  
Prior Work ◽  
Serovar Typhimurium ◽  
Thiamine Biosynthesis

ABSTRACT Work presented here establishes a connection between cellular coenzyme A (CoA) levels and thiamine biosynthesis in Salmonella enterica serovar Typhimurium. Prior work showed thatpanE mutants (panE encodes ketopantoate reductase) had a conditional requirement for thiamine or pantothenate. Data presented herein show that the nutritional requirement ofpanE mutants for either thiamine or pantothenate is manifest only when flux through the purine biosynthetic pathway is reduced. Further, the data show that under the above conditions it is the lack of thiamine pyrophosphate, and not decreased CoA levels, that directly prevents growth.

scholarly journals The Salmonella enterica Serovar Typhimurium Divalent Cation Transport Systems MntH and SitABCD Are Essential for Virulence in an Nramp1G169 Murine Typhoid Model

2004 ◽  
Vol 72 (9) ◽  
pp. 5522-5525 ◽  
Author(s):  
Michelle L. Zaharik ◽  
Vivian Li Cullen ◽  
Angela M. Fung ◽  
Stephen J. Libby ◽  
Sonya L. Kujat Choy ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Metal Ion ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Divalent Cations ◽  
Systemic Infection ◽  
Transport Systems ◽  
Phagocytic Cells ◽  
Serovar Typhimurium ◽  
Genes Encoding ◽  
Metal Ion Uptake

ABSTRACT Nramp1 is a transporter that pumps divalent cations from the vacuoles of phagocytic cells and is associated with the innate resistance of mice to diverse intracellular pathogens. We demonstrate that sitA and mntH, genes encoding high-affinity metal ion uptake systems in Salmonella enterica serovar Typhimurium, are upregulated when Salmonella is internalized by Nramp1-expressing macrophages and play an essential role in systemic infection of congenic Nramp1-expressing mice.

scholarly journals Removal of the phage-shock protein PspB causes reduction of virulence in Salmonella enterica serovar Typhimurium independently of NRAMP1

2014 ◽  
Vol 63 (6) ◽  
pp. 788-795 ◽  
Author(s):  
Inke Wallrodt ◽  
Lotte Jelsbak ◽  
Line E. Thomsen ◽  
Lena Brix ◽  
Sébastien Lemire ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Single Gene ◽  
Systemic Infection ◽  
Minor Effect ◽  
Membrane Stress ◽  
Knock Out ◽  
Serovar Typhimurium ◽  
A Minor

The phage-shock protein (Psp) system is believed to manage membrane stress in all Enterobacteriaceae and has recently emerged as being important for virulence in several pathogenic species of this phylum. The core of the Psp system consists of the pspA–D operon and the distantly located pspG gene. In Salmonella enterica serovar Typhimurium (S. Typhimurium), it has recently been reported that PspA is essential for systemic infection of mice, but only in NRAMP1+ mice, signifying that attenuation is related to coping with divalent cation starvation in the intracellular environment. In the present study, we investigated the contribution of individual psp genes to virulence of S. Typhimurium. Interestingly, deletion of the whole pspA–D set of genes caused attenuation in both NRAMP1+ and NRAMP1− mice, indicating that one or more of the psp genes contribute to virulence independently of NRAMP1 expression in the host. Investigations of single gene mutants showed that knock out of pspB reduced virulence in both types of mice, while deletion of pspA only caused attenuation in NRAMP1+ mice, and deletion of pspD had a minor effect in NRAMP1− mice, while deletions of either pspC or pspG did not affect virulence. Experiments addressed at elucidating the role of PspB in virulence revealed that PspB is dispensable for uptake to and intracellular replication in cultured macrophages and resistance to complement-induced killing. Furthermore, the Psp system of S. Typhimurium was dispensable during pIV-induced secretin stress. In conclusion, our results demonstrate that removal of PspB reduces virulence in S. Typhimurium independently of host NRAMP1 expression, demonstrating that PspB has roles in intra-host survival distinct from the reported contributions of PspA.

scholarly journals Salmonella enterica Serovar Typhimurium Requires Nonsterol Precursors of the Cholesterol Biosynthetic Pathway for Intracellular Proliferation

2004 ◽  
Vol 72 (2) ◽  
pp. 1036-1042 ◽  
Author(s):  
Drew M. Catron ◽  
Yvonne Lange ◽  
Jayme Borensztajn ◽  
Matthew D. Sylvester ◽  
Bradley D. Jones ◽  
...  
Keyword(s):  
Mouse Model ◽  
Host Cell ◽  
Bacterial Growth ◽  
Salmonella Enterica ◽  
Biosynthetic Pathway ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Bacterial Proliferation ◽  
Serovar Typhimurium ◽  
Cholesterol Biosynthetic Pathway ◽  
Intracellular Proliferation

ABSTRACT We have previously shown that Salmonella enterica serovar Typhimurium infection perturbs the host cholesterol biosynthetic pathway. Here we show that inhibiting the first step of this pathway (3-hydroxy-3-methylglutaryl coenzyme A reductase) reduces the growth of intracellular S. enterica serovar Typhimurium and has no effect on extracellular bacterial growth. Selectively inhibiting synthesis of downstream sterol components has no effect on infection, suggesting that the effect of statins on host nonsterol intermediates is detrimental to bacterial growth. Furthermore, statins also reduce bacterial proliferation in the S. enterica serovar Typhimurium mouse model. This suggests that blocking the production of nonsterol precursors in the host cell can be used to reduce infection.

scholarly journals Lon, a Stress-Induced ATP-Dependent Protease, Is Critically Important for Systemic Salmonella enterica Serovar Typhimurium Infection of Mice

2003 ◽  
Vol 71 (2) ◽  
pp. 690-696 ◽  
Author(s):  
Akiko Takaya ◽  
Masato Suzuki ◽  
Hidenori Matsui ◽  
Toshifumi Tomoyasu ◽  
Hiroshi Sashinami ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Disease ◽  
Systemic Infection ◽  
Lon Protease ◽  
Phagocytic Cells ◽  
Disruption Mutant ◽  
Systemic Spread ◽  
Serovar Typhimurium ◽  
Increased Sensitivity

ABSTRACT Studies on the pathogenesis of Salmonella enterica serovar Typhimurium infections in mice have revealed the presence of two prominent virulence characteristics—the invasion of the nonphagocytic cells to penetrate the intestinal epithelium and the proliferation within host phagocytic cells to cause a systemic spread and the colonization of host organs. We have recently demonstrated that the ATP-dependent Lon protease of S. enterica serovar Typhimurium negatively regulates the efficiency of invasion of epithelial cells and the expression of invasion genes (A. Takaya et al., J. Bacteriol. 184:224-232, 2002). This study was performed to reveal the contribution of the Lon protease to the virulence of S. enterica serovar Typhimurium in mice. Determination of 50% lethal doses for the lon disruption mutant and wild-type strain revealed that the mutant was highly attenuated when administered either orally or intraperitoneally to BALB/c mice. The mutant was also found to be able to reach extraintestinal sites but unable to proliferate efficiently within the spleen and cause lethal systemic disease of mice. Macrophage survival assays revealed that the lon disruption mutant could not survive or proliferate within murine macrophages. In addition, the mutant showed extremely increased susceptibility to hydrogen peroxide, which contributes to the bactericidal capacity of phagocytes. The mutant also showed increased sensitivity to acidic conditions. Taken together, the impaired ability of the lon disruption mutant to survive and grow in macrophages could be due to the enhanced susceptibility to the oxygen-dependent killing mechanism associated with respiratory burst and the low phagosomal pH. These results suggest that the Lon protease is essentially involved in the systemic infection of mice with S. enterica serovar Typhimurium, which can be fatal. Of further interest is the finding that the lon disruption mutant persists in the BALB/c mice for long periods without causing an overwhelming systemic infection.

scholarly journals Coordinated Regulation of Virulence during Systemic Infection of Salmonella enterica Serovar Typhimurium

2009 ◽  
Vol 5 (2) ◽  
pp. e1000306 ◽  
Author(s):  
Hyunjin Yoon ◽  
Jason E. McDermott ◽  
Steffen Porwollik ◽  
Michael McClelland ◽  
Fred Heffron
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Systemic Infection ◽  
Serovar Typhimurium ◽  
Coordinated Regulation
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