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 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 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 Genetic Analysis of Colistin Resistance in Salmonella enterica Serovar Typhimurium

2009 ◽  
Vol 53 (6) ◽  
pp. 2298-2305 ◽  
Author(s):  
Song Sun ◽  
Aurel Negrea ◽  
Mikael Rhen ◽  
Dan I. Andersson
Keyword(s):  
Mutation Rate ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory System ◽  
Clinical Settings ◽  
Missense Mutations ◽  
Regulator Protein ◽  
Serovar Typhimurium ◽  
Sensor Kinases ◽  
Genes Encoding

ABSTRACT Colistin is a cyclic cationic peptide that kills gram-negative bacteria by interacting with and disrupting the outer membrane. We isolated 44 independent mutants in Salmonella enterica serovar Typhimurium with reduced susceptibility to colistin and identified 27 different missense mutations located in the pmrA and pmrB genes (encoding the regulator and sensor of a two-component regulatory system) that conferred increased resistance. By comparison of the two homologous sensor kinases, PmrB and EnvZ, the 22 missense mutations identified in pmrB were shown to be located in four different structural domains of the protein. All five pmrA mutations were located in the phosphate receiver domain of the regulator protein. The mutants appeared at a mutation rate of 0.6 × 10−6 per cell per generation. The MICs of colistin for the mutants increased 2- to 35-fold, and the extent of killing was reduced several orders of magnitude compared to the susceptible strain. The growth rates of the mutants were slightly reduced in both rich medium and M9-glycerol minimal medium, whereas growth in mice appeared unaffected by the pmrA and pmrB mutations. The low fitness costs and the high mutation rate suggest that mutants with reduced susceptibility to colistin could emerge in clinical settings.

scholarly journals Role of Toll-Like Receptor 4 in Macrophage Activation and Tolerance during Salmonella enterica Serovar Typhimurium Infection

2003 ◽  
Vol 71 (9) ◽  
pp. 4873-4882 ◽  
Author(s):  
Qian Li ◽  
Bobby J. Cherayil
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Peritoneal Macrophages ◽  
Phagocytic Cells ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Serovar Typhimurium ◽  
Tlr4 Gene ◽  
Factor Alpha

ABSTRACT Toll-like receptors (TLRs) play an important role in the innate immune response, particularly in the initial interaction between the infecting microorganism and phagocytic cells, such as macrophages. We investigated the role of TLR4 during infection of primary murine peritoneal macrophages with Salmonella enterica serovar Typhimurium. We found that macrophages from the C3H/HeJ mouse strain, which carries a functionally inactive Tlr4 gene, exhibit marked impairment of tumor necrosis factor alpha (TNF-α) secretion in response to S. enterica serovar Typhimurium infection. However, activation of extracellular growth factor-regulated kinase and NF-κB signaling pathways was relatively unaffected, as was increased expression of TNF-α mRNA. Furthermore, macrophage tolerance, which is associated with increased expression of the NF-κB p50 and p52 subunits, was induced by S. enterica serovar Typhimurium even in the absence of functional TLR4. These results indicate that during infection of macrophages by S. enterica serovar Typhimurium, TLR4 signals are required at a posttranscriptional step to maximize secretion of TNF-α. Signals delivered by pattern recognition receptors other than TLR4 are sufficient for the increased expression of the TNF-α transcript and at least some genes associated with macrophage tolerance.

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 MntP and YiiP Contribute to Manganese Efflux in Salmonella enterica Serovar Typhimurium under Conditions of Manganese Overload and Nitrosative Stress

2022 ◽  
Author(s):  
Annie Ouyang ◽  
Kendall M. Gasner ◽  
Stephanie L. Neville ◽  
Christopher A. McDevitt ◽  
Elaine R. Frawley
Keyword(s):  
Transition Metal ◽  
Salmonella Enterica ◽  
Metal Ion ◽  
Nitrosative Stress ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Metal Cations ◽  
Transition Metal Cations ◽  
Bacterial Physiology ◽  
Area Of Interest ◽  
Serovar Typhimurium

Transition metal cations are required for the function of many proteins but can mediate toxicity when present in excess. Identifying transporters that facilitate metal ion export, the conditions under which they are expressed, and the role they play in bacterial physiology is an evolving area of interest for environmental and pathogenic organisms.

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 Role of the High-Affinity Zinc Uptake znuABC System in Salmonella enterica Serovar Typhimurium Virulence

2002 ◽  
Vol 70 (8) ◽  
pp. 4721-4725 ◽  
Author(s):  
Susana Campoy ◽  
Mónica Jara ◽  
Núria Busquets ◽  
Ana M. Pérez de Rozas ◽  
Ignacio Badiola ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Lethal Dose ◽  
Zinc Uptake ◽  
Uptake System ◽  
High Affinity ◽  
Knockout Mutants ◽  
Serovar Typhimurium ◽  
Genes Encoding

ABSTRACT The Salmonella enterica serovar Typhimurium znuABC genes encoding a high-affinity zinc uptake system and its regulatory zur gene have been cloned. Salmonella serovar Typhimurium zur and znuC knockout mutants have been constructed by marker exchange. The 50% lethal dose of the znuC mutant increased when either orally or intraperitoneally inoculated in BALB/c mice, while virulence of the zur mutant decreased only when mice were intraperitoneally challenged.

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