scholarly journals FNR Is a Global Regulator of Virulence and Anaerobic Metabolism in Salmonella enterica Serovar Typhimurium (ATCC 14028s)

2007 ◽  
Vol 189 (6) ◽  
pp. 2262-2273 ◽  
Author(s):  
Ryan C. Fink ◽  
Matthew R. Evans ◽  
Steffen Porwollik ◽  
Andres Vazquez-Torres ◽  
Jessica Jones-Carson ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Protein A ◽  
Stress Protein ◽  
Carbon Utilization ◽  
E Coli ◽  
Flagellar Biosynthesis ◽  
Serovar Typhimurium ◽  
Phagocyte Oxidase

ABSTRACT Salmonella enterica serovar Typhimurium must successfully transition the broad fluctuations in oxygen concentrations encountered in the host. In Escherichia coli, FNR is one of the main regulatory proteins involved in O2 sensing. To assess the role of FNR in serovar Typhimurium, we constructed an isogenic fnr mutant in the virulent wild-type strain (ATCC 14028s) and compared their transcriptional profiles and pathogenicities in mice. Here, we report that, under anaerobic conditions, 311 genes (6.80% of the genome) are regulated directly or indirectly by FNR; of these, 87 genes (28%) are poorly characterized. Regulation by FNR in serovar Typhimurium is similar to, but distinct from, that in E. coli. Thus, genes/operons involved in aerobic metabolism, NO· detoxification, flagellar biosynthesis, motility, chemotaxis, and anaerobic carbon utilization are regulated by FNR in a fashion similar to that in E. coli. However, genes/operons existing in E. coli but regulated by FNR only in serovar Typhimurium include those coding for ethanolamine utilization, a universal stress protein, a ferritin-like protein, and a phosphotransacetylase. Interestingly, Salmonella-specific genes/operons regulated by FNR include numerous virulence genes within Salmonella pathogenicity island 1 (SPI-1), newly identified flagellar genes (mcpAC, cheV), and the virulence operon (srfABC). Furthermore, the role of FNR as a positive regulator of motility, flagellar biosynthesis, and pathogenesis was confirmed by showing that the mutant is nonmotile, lacks flagella, is attenuated in mice, and does not survive inside macrophages. The inability of the mutant to survive inside macrophages is likely due to its sensitivity to the reactive oxygen species generated by NADPH phagocyte oxidase.

scholarly journals Arginine-Dependent Acid Resistance in Salmonella enterica Serovar Typhimurium

2006 ◽  
Vol 188 (15) ◽  
pp. 5650-5653 ◽  
Author(s):  
Jasper Kieboom ◽  
Tjakko Abee
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Acid Resistance ◽  
Arginine Decarboxylase ◽  
Acidic Ph ◽  
E Coli ◽  
Serovar Typhimurium ◽  
Microaerobic Conditions ◽  
Acid Challenge

ABSTRACT Salmonella enterica serovar Typhimurium does not survive a pH 2.5 acid challenge under conditions similar to those used for Escherichia coli (J. W. Foster, Nat. Rev. Microbiol. 2:898-907, 2004). Here, we provide evidence that S. enterica serovar Typhimurium can display arginine-dependent acid resistance (AR) provided the cells are grown under anoxic conditions and not under the microaerobic conditions used for assessment of AR in E. coli. The role of the arginine decarboxylase pathway in Salmonella AR was shown by the loss of AR in mutants lacking adiA, which encodes arginine decarboxylase; adiC, which encodes the arginine-agmatine antiporter; or adiY, which encodes an AraC-like regulator. Transcription of adiA and adiC was found to be dependent on AdiY, anaerobiosis, and acidic pH.

scholarly journals Constitutive Acid Sphingomyelinase Enhances Early and Late Macrophage Killing of Salmonella enterica Serovar Typhimurium

2007 ◽  
Vol 75 (11) ◽  
pp. 5346-5352 ◽  
Author(s):  
Bruce D. McCollister ◽  
Jesse T. Myers ◽  
Jessica Jones-Carson ◽  
Dennis R. Voelker ◽  
Andrés Vázquez-Torres
Keyword(s):  
Type Iii Secretion ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Acid Sphingomyelinase ◽  
Wild Type ◽  
Serovar Typhimurium ◽  
Important Player ◽  
Phagocyte Oxidase ◽  
Macrophage Killing

ABSTRACT We have identified acid sphingomyelinase (ASM) as an important player in the early and late anti-Salmonella activity of macrophages. A functional ASM participated in the killing activity of macrophages against wild-type Salmonella enterica serovar Typhimurium. The role of ASM in early macrophage killing of Salmonella appears to be linked to an active NADPH phagocyte oxidase enzymatic complex, since the flavoprotein inhibitor diphenyleneiodonium not only blocked a productive respiratory burst but also abrogated the survival advantage of Salmonella in macrophages lacking ASM. Lack of ASM activity also increased the intracellular survival of an isogenic ΔspiC::FRT Salmonella strain deficient in a translocator and effector of the Salmonella pathogenicity island 2 (SPI2) type III secretion system, suggesting that the antimicrobial activity associated with ASM is manifested regardless of the SPI2 status of the bacteria. Constitutively expressed ASM is responsible for the role that this lipid-metabolizing hydrolase plays in the innate host defense of macrophages against Salmonella. Accordingly, the ASM activity and intracellular concentration and composition of ceramide, gangliosides, and neutral sphingolipids did not increase upon Salmonella infection. Salmonella triggered, nonetheless, a significant increase in the secreted fraction of ASM. Collectively, these findings have elucidated a novel role for constitutive ASM in the anti-Salmonella activity of murine macrophages.

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.

Detection of Escherichia coli O157, Salmonella enterica Serovar Typhimurium, and Staphylococcal Enterotoxin B in a Single Sample Using Enzymatic Bio-Nanotransduction

2007 ◽  
Vol 70 (4) ◽  
pp. 841-850 ◽  
Author(s):  
JOSH R. BRANEN ◽  
MARTHA J. HASS ◽  
ERIN R. DOUTHIT ◽  
WUSI C. MAKI ◽  
A. LARRY BRANEN
Keyword(s):  
Escherichia Coli ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Staphylococcal Enterotoxin B ◽  
Escherichia Coli O157 ◽  
Dna Templates ◽  
E Coli ◽  
Serovar Typhimurium ◽  
Biological Recognition ◽  
Enterotoxin B

Enzymatic bio-nanotransduction is a biological detection scheme based on the production of nucleic acid nano-signals (RNA) in response to specific biological recognition events. In this study, we applied an enzymatic bio-nanotransduction system to the detection of important food-related pathogens and a toxin. Escherichia coli O157:H7, Salmonella enterica serovar Typhimurium, and staphylococcal enterotoxin B (SEB) were chosen because of the implications of these targets to food safety. Primary antibodies to each of the targets were used to functionalize magnetic beads and produce biological recognition elements (antibodies) conjugated to nano-signal–producing DNA templates. Immunomagnetic capture that was followed by in vitro transcription of DNA templates bound to target molecules produced RNA nano-signals specific for every target in the sample. Discrimination of RNA nano-signals with a standard enzyme-linked oligonucleotide fluorescence assay provided a correlation between nano-signal profiles and target concentrations. The estimated limit of detection was 2.4 × 103 CFU/ml for E. coli O157:H7, 1.9 × 104 CFU/ml for S. enterica serovar Typhimurium, and 0.11 ng/ml for SEB with multianalyte detection in buffer. Low levels of one target were also detected in the presence of interference from high levels of the other targets. Finally, targets were detected in milk, and detection was improved for E. coli O157 by heat treatment of the milk.

scholarly journals Salmonella enterica Serovar Typhimurium and Escherichia coli Survival in Estuarine Bank Sediments

2018 ◽  
Vol 15 (11) ◽  
pp. 2597 ◽  
Author(s):  
Mahbubul Siddiqee ◽  
Rebekah Henry ◽  
Rebecca Coulthard ◽  
Christelle Schang ◽  
Richard Williamson ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Growth Patterns ◽  
Estuarine Sediments ◽  
Human Pathogens ◽  
Indicator Organisms ◽  
Fecal Indicator ◽  
E Coli ◽  
Serovar Typhimurium

Estuarine bank sediments have the potential to support the survival and growth of fecal indicator organisms, including Escherichia coli. However, survival of fecal pathogens in estuarine sediments is not well researched and therefore remains a significant knowledge gap regarding public health risks in estuaries. In this study, simultaneous survival of Escherichia coli and a fecal pathogen, Salmonella enterica serovar Typhimurium, was studied for 21 days in estuarine bank sediment microcosms. Observed growth patterns for both organisms were comparable under four simulated scenarios; for continuous-desiccation, extended-desiccation, periodic-inundation, and continuous-inundation systems, logarithmic decay coefficients were 1.54/day, 1.51/day, 0.14/day, and 0.20/day, respectively, for E. coli, and 1.72/day, 1.64/day, 0.21/day, and 0.24/day for S. Typhimurium. Re-wetting of continuous-desiccated systems resulted in potential re-growth, suggesting survival under moisture-limited conditions. Key findings from this study include: (i) Bank sediments can potentially support human pathogens (S. Typhimurium), (ii) inundation levels influence the survival of fecal bacteria in estuarine bank sediments, and (iii) comparable survival rates of S. Typhimurium and E. coli implies the latter could be a reliable fecal indicator in urban estuaries. The results from this study will help select suitable monitoring and management strategies for safer recreational activities in urban estuaries.

scholarly journals Flagella and Chemotaxis Are Required for Efficient Induction of Salmonella enterica Serovar Typhimurium Colitis in Streptomycin-Pretreated Mice

2004 ◽  
Vol 72 (7) ◽  
pp. 4138-4150 ◽  
Author(s):  
Bärbel Stecher ◽  
Siegfried Hapfelmeier ◽  
Catherine Müller ◽  
Marcus Kremer ◽  
Thomas Stallmach ◽  
...  
Keyword(s):  
Virulence Factors ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Innate Immune ◽  
Gastrointestinal Infections ◽  
Infection Models ◽  
Serovar Typhimurium ◽  
Efficient Induction ◽  
Toll Like Receptor 5

ABSTRACT Salmonella enterica subspecies 1 serovar Typhimurium is a common cause of gastrointestinal infections. The host's innate immune system and a complex set of Salmonella virulence factors are thought to contribute to enteric disease. The serovar Typhimurium virulence factors have been studied extensively by using tissue culture assays, and bovine infection models have been used to verify the role of these factors in enterocolitis. Streptomycin-pretreated mice provide an alternative animal model to study enteric salmonellosis. In this model, the Salmonella pathogenicity island 1 type III secretion system has a key virulence function. Nothing is known about the role of other virulence factors. We investigated the role of flagella in murine serovar Typhimurium colitis. A nonflagellated serovar Typhimurium mutant (fliGHI) efficiently colonized the intestine but caused little colitis during the early phase of infection (10 and 24 h postinfection). In competition assays with differentially labeled strains, the fliGHI mutant had a reduced capacity to get near the intestinal epithelium, as determined by fluorescence microscopy. A flagellated but nonchemotactic cheY mutant had the same virulence defects as the fliGHI mutant for causing colitis. In competitive infections, both mutants colonized the intestine of streptomycin-pretreated mice by day 1 postinfection but were outcompeted by the wild-type strain by day 3 postinfection. Together, these data demonstrate that flagella are required for efficient colonization and induction of colitis in streptomycin-pretreated mice. This effect is mostly attributable to chemotaxis. Recognition of flagellar subunits (i.e., flagellin) by innate immune receptors (i.e., Toll-like receptor 5) may be less important.

scholarly journals The Multi-Copper-Ion Oxidase CueO of Salmonella enterica Serovar Typhimurium Is Required for Systemic Virulence

2010 ◽  
Vol 78 (5) ◽  
pp. 2312-2319 ◽  
Author(s):  
Maud E. S. Achard ◽  
Jai J. Tree ◽  
James A. Holden ◽  
Kim R. Simpfendorfer ◽  
Odilia L. C. Wijburg ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Copper Ions ◽  
Copper Ion ◽  
Mesenteric Lymph Nodes ◽  
E Coli ◽  
Significant Difference ◽  
Serovar Typhimurium ◽  
Branched Chain ◽  
Periplasmic Enzyme

ABSTRACT Salmonella enterica serovar Typhimurium possesses a multi-copper-ion oxidase (multicopper oxidase), CueO (also known as CuiD), a periplasmic enzyme known to be required for resistance to copper ions. CueO from S. Typhimurium was expressed as a recombinant protein in Escherichia coli, and the purified protein exhibited a high cuprous oxidase activity. We have characterized an S. Typhimurium cueO mutant and confirmed that it is more sensitive to copper ions. Using a murine model of infection, it was observed that the cueO mutant was significantly attenuated, as indicated by reduced recovery of bacteria from liver and spleen, although there was no significant difference in recovery from Peyer's patches and mesenteric lymph nodes. However, the intracellular survival of the cueO mutant in unprimed or gamma-interferon-primed murine macrophages was not statistically different from that of wild-type Salmonella, suggesting that additional host factors are involved in clearance of the cueO mutant. Unlike a cueO mutant from E. coli, the S. Typhimurium cueO mutant did not show greater sensitivity to hydrogen peroxide and its sensitivity to copper ions was not affected by siderophores. Similarly, the S. Typhimurium cueO mutant was not rescued from copper ion toxicity by addition of the branched-chain amino acids and leucine.

scholarly journals Role of the alternative sigma factors σ E and σ S in survival of Salmonella enterica serovar Typhimurium during starvation, refrigeration and osmotic shock

Microbiology ◽  
2007 ◽  
Vol 153 (1) ◽  
pp. 263-269 ◽  
Author(s):  
Alisdair McMeechan ◽  
Mark Roberts ◽  
Tristan A. Cogan ◽  
Frieda Jørgensen ◽  
Andrew Stevenson ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Osmotic Shock ◽  
Sigma Factors ◽  
Alternative Sigma Factors ◽  
Serovar Typhimurium

scholarly journals The enzyme phosphoglucomutase (Pgm) is required by Salmonella enterica serovar Typhimurium for O-antigen production, resistance to antimicrobial peptides and in vivo fitness

Microbiology ◽  
2009 ◽  
Vol 155 (10) ◽  
pp. 3403-3410 ◽  
Author(s):  
G. K. Paterson ◽  
D. B. Cone ◽  
S. E. Peters ◽  
D. J. Maskell
Keyword(s):  
Antimicrobial Peptides ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Live Attenuated Vaccine ◽  
Antigen Production ◽  
O Antigen ◽  
Serovar Typhimurium

The enzyme phosphoglucomutase (Pgm) catalyses the interconversion of glucose 1-phosphate and glucose 6-phosphate and contributes to glycolysis and the generation of sugar nucleotides for biosynthesis. To assess the role of this enzyme in the biology of the pathogen Salmonella enterica serovar Typhimurium we have characterized a pgm deletion mutant in strain SL1344. Compared to SL1344, SL1344 pgm had impaired growth in vitro, was deficient in the ability to utilize galactose as a carbon source and displayed reduced O-antigen polymer length. The mutant was also more susceptible to antimicrobial peptides and showed decreased fitness in the mouse typhoid model. The in vivo phenotype of SL1344 pgm indicated a role for pgm in the early stages of infection, most likely through deficient O-antigen production. Although pgm mutants in other pathogens have potential as live attenuated vaccine strains, SL1344 pgm was not sufficiently attenuated for such use.

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