scholarly journals Nucleoid-associated protein HU controls three regulons that coordinate virulence, response to stress and general physiology in Salmonella enterica serovar Typhimurium

Microbiology ◽  
2011 ◽  
Vol 157 (4) ◽  
pp. 1075-1087 ◽  
Author(s):  
Michael W. Mangan ◽  
Sacha Lucchini ◽  
Tadhg Ó Cróinín ◽  
Stephen Fitzgerald ◽  
Jay C. D. Hinton ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Double Mutant ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Expression Of Genes ◽  
Hu Proteins ◽  
Epithelial Cell Lines ◽  
Serovar Typhimurium ◽  
Associated Proteins ◽  
Response To Stress

The role of the HU nucleoid-associated proteins in gene regulation was examined in Salmonella enterica serovar Typhimurium. The dimeric HU protein consists of different combinations of its α and β subunits. Transcriptomic analysis was performed with cultures growing at 37 °C at 1, 4 and 6 h after inoculation with mutants that lack combinations of HU α and HU β. Distinct but overlapping patterns of gene expression were detected at each time point for each of the three mutants, revealing not one but three regulons of genes controlled by the HU proteins. Mutations in the hup genes altered the expression of regulatory and structural genes in both the SPI1 and SPI2 pathogenicity islands. The hupA hupB double mutant was defective in invasion of epithelial cell lines and in its ability to survive in macrophages. The double mutant also had defective swarming activity and a competitive fitness disadvantage compared with the wild-type. In contrast, inactivation of just the hupB gene resulted in increased fitness and correlated with the upregulation of members of the RpoS regulon in exponential-phase cultures. Our data show that HU coordinates the expression of genes involved in central metabolism and virulence and contributes to the success of S. enterica as a pathogen.

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 A Salmonella enterica Serovar Typhimurium Succinate Dehydrogenase/Fumarate Reductase Double Mutant Is Avirulent and Immunogenic in BALB/c Mice

2007 ◽  
Vol 76 (3) ◽  
pp. 1128-1134 ◽  
Author(s):  
Regino Mercado-Lubo ◽  
Eric J. Gauger ◽  
Mary P. Leatham ◽  
Tyrrell Conway ◽  
Paul S. Cohen
Keyword(s):  
Succinate Dehydrogenase ◽  
Salmonella Enterica ◽  
Double Mutant ◽  
Wild Type Strain ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Tca Cycle ◽  
Fumarate Reductase ◽  
Subsequent Infection ◽  
The Tca Cycle ◽  
Serovar Typhimurium

ABSTRACT Previously we showed that the tricarboxylic acid (TCA) cycle operates as a full cycle during Salmonella enterica serovar Typhimurium SR-11 peroral infection of BALB/c mice (M. Tchawa Yimga et al., Infect. Immun. 74:1130-1140, 2006). The evidence was that a ΔsucCD mutant (succinyl coenzyme A [succinyl-CoA] synthetase), which prevents the conversion of succinyl-CoA to succinate, and a ΔsdhCDA mutant (succinate dehydrogenase), which blocks the conversion of succinate to fumarate, were both attenuated, whereas an SR-11 ΔaspA mutant (aspartase) and an SR-11 ΔfrdABCD mutant (fumarate reductase), deficient in the ability to run the reductive branch of the TCA cycle, were fully virulent. In the present study, evidence is presented that a serovar Typhimurium SR-11 ΔfrdABCD ΔsdhCDA double mutant is avirulent in BALB/c mice and protective against subsequent infection with the virulent serovar Typhimurium SR-11 wild-type strain via the peroral route and is highly attenuated via the intraperitoneal route. These results suggest that fumarate reductase, which normally runs in the reductive pathway in the opposite direction of succinate dehydrogenase, can replace it during infection by running in the same direction as succinate dehydrogenase in order to run a full TCA cycle in an SR-11 ΔsdhCDA mutant. The data also suggest that the conversion of succinate to fumarate plays a key role in serovar Typhimurium virulence. Moreover, the data raise the possibility that S. enterica ΔfrdABCD ΔsdhCDA double mutants and ΔfrdABCD ΔsdhCDA double mutants of other intracellular bacterial pathogens with complete TCA cycles may prove to be effective live vaccine strains for animals and humans.

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 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.

scholarly journals Role of SPI-1 Secreted Effectors in Acute Bovine Response to Salmonella enterica Serovar Typhimurium: A Systems Biology Analysis Approach

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e26869 ◽  
Author(s):  
Sara D. Lawhon ◽  
Sangeeta Khare ◽  
Carlos A. Rossetti ◽  
Robin E. Everts ◽  
Cristi L. Galindo ◽  
...  
Keyword(s):  
Systems Biology ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Analysis Approach ◽  
Serovar Typhimurium

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 Altering the Length of the Lipopolysaccharide O Antigen Has an Impact on the Interaction of Salmonella enterica Serovar Typhimurium with Macrophages and Complement

2006 ◽  
Vol 188 (7) ◽  
pp. 2735-2739 ◽  
Author(s):  
Gerald L. Murray ◽  
Stephen R. Attridge ◽  
Renato Morona
Keyword(s):  
Vibrio Cholerae ◽  
Salmonella Enterica ◽  
Double Mutant ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Shigella Flexneri ◽  
O Antigen ◽  
Repeat Units ◽  
Complement Resistance ◽  
Serovar Typhimurium ◽  
First Time

ABSTRACT A panel of isogenic Salmonella enterica serovar Typhimurium strains that vary only in the length of the O antigen was constructed through complementation of a wzz double mutant (displaying unregulated O-antigen length) with one of two homologous (wzz ST and wzz fepE) or three heterologous (wzz O139 of Vibrio cholerae and wzz SF and wzz pHS-2 of Shigella flexneri) wzz genes. Each gene was functional in the S. enterica serovar Typhimurium host and specified production of O-antigen polymers with lengths typical of those synthesized by the donor bacteria (ranging from 2 to >100 O-antigen repeat units). By use of this panel of strains, it was found that O-antigen length influences invasion/uptake by macrophage cells; this is the first time this has been shown with Salmonella. O-antigen length was confirmed to be related to complement resistance, with a minimum protective length of >4 and <15 repeat units. O antigen of 16 to 35 repeat units was found to activate complement more efficiently than other lengths, but this was unrelated to complement resistance. No evidence was found to suggest that modifying the length of the O-antigen polymer affected expression of the O1, O4, or O5 antigenic factors.

scholarly journals Disruption of Epithelial Barrier Integrity by Salmonella enterica Serovar Typhimurium Requires Geranylgeranylated Proteins

2003 ◽  
Vol 71 (2) ◽  
pp. 872-881 ◽  
Author(s):  
Farideh Tafazoli ◽  
Karl-Eric Magnusson ◽  
Limin Zheng
Keyword(s):  
Epithelial Cells ◽  
Salmonella Enterica ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Epithelial Barrier ◽  
Phosphatidylinositol 3 Kinase ◽  
Barrier Integrity ◽  
Actin Organization ◽  
Rho Family Gtpases ◽  
Serovar Typhimurium ◽  
Associated Proteins

ABSTRACT Epithelial cells that line the human intestinal mucosa constitute the initial sites of host invasion by bacterial pathogens. A number of bacteria, such as Salmonella and Yersinia spp., have been shown to disrupt the integrity of the epithelial barrier, although little is known about the mechanisms underlying that effect. We found that polarized MDCK-1 epithelial cells infected with invasive Salmonella enterica serovar Typhimurium SL1344 exhibited marked changes in F-actin organization, an increase in the paracellular flux of dextran, and a rapid decrease in transepithelial electrical resistance (TER). In contrast, infection with an isogenic noninvasive mutant (hilA) increased the TER in these cells. Pretreating MDCK-1 cells with the inhibitors for tyrosine kinase (genistein) or phosphatidylinositol 3-kinase (wortmannin) did not affect invasion and subsequent perturbation of the epithelial barrier by serovar Typhimurium. Instead, the geranylgeranyltransferase 1 inhibitor GGTI-298, but not the farnesyltransferase inhibitor FTI-277, clearly reversed the capacity of serovar Typhimurium to disrupt the epithelial barrier. The substrates for GGTI-298 include Rho family GTPases, as indicated by inhibiting prenylation of Rac1 and Cdc42. Infection with wild-type serovar Typhimurium increased the level of activated Rac1 and Cdc42 and caused these proteins to accumulate apically in MDCK-1 cells. This Salmonella-induced accumulation of Rac1 and Cdc42 and alteration of the junction-associated proteins ZO-1, occludin, and E-cadherin in MDCK-1 cells were markedly inhibited by GGTI-298. These results suggest that activation of geranylgeranylated proteins, including Rac1 and Cdc42, is critical for disruption of barrier integrity by serovar Typhimurium in polarized MDCK-1 cells.

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