TheSalmonella entericaSerovar Typhimurium Divalent Cation Transport Systems MntH and SitABCD Are Essential for Virulence in anNramp1G169Murine Typhoid Model

Zaharik, Michelle L.; Cullen, Vivian Li; Fung, Angela M.; Libby, Stephen J.; Choy, Sonya L. Kujat; Coburn, Bryan; Kehres, David G.; Maguire, Michael E.; Fang, Ferric C.; Finlay, B. Brett

doi:10.1128/iai.72.9.5522-5525.2004

Cited by 114 publications

(107 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with those results, sit appears to be induced in mice after invasion of the intestinal mucosa (18) and after uptake by macrophage cells in culture (41). Similarly, mntH is not involved in the invasion of HeLa cells, and the expression of mntH is induced after phagocytosis by macrophages (22,41). Virulence studies show a clear role for both sit and mntH during infection (4,18,21,41).…”

supporting

confidence: 67%

“…Although the genes encoding SitABCD are located in the pathogenicity island SPI-1, responsible for invasion of epithelial cells, the sit operon does not appear to be involved in invasion (18,41,43). Consistent with those results, sit appears to be induced in mice after invasion of the intestinal mucosa (18) and after uptake by macrophage cells in culture (41). Similarly, mntH is not involved in the invasion of HeLa cells, and the expression of mntH is induced after phagocytosis by macrophages (22,41).…”

mentioning

confidence: 99%

“…Similarly, mntH is not involved in the invasion of HeLa cells, and the expression of mntH is induced after phagocytosis by macrophages (22,41). Virulence studies show a clear role for both sit and mntH during infection (4,18,21,41). A virulence defect is particularly evident when both Mn transporters are mutated (4,41).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Transcriptional Regulation ofsitABCDofSalmonella entericaSerovar Typhimurium by MntR and Fur

Ikeda¹,

Janakiraman²,

Kehres

et al. 2005

J Bacteriol

Self Cite

112

View full text Add to dashboard Cite

Salmonella enterica serovar Typhimurium has two manganese transport systems, MntH and SitABCD. MntH is a bacterial homolog of the eukaryotic natural resistance-associated macrophage protein 1 (Nramp1), and SitABCD is an ABC-type transporter. Previously we showed that mntH is negatively controlled at the transcriptional level by the trans-acting regulatory factors, MntR and Fur. In this study, we examined the transcriptional regulation of sitABCD and compared it to the transcriptional regulation of mntH by constructing lacZ fusions to the promoter regions with and without mutations in putative MntR and/or Fur binding sites. The presence of Mn caused transcriptional repression of the sitABCD and mntH promoters primarily via MntR, but Fur was also capable of some repression in response to Mn. Likewise, Fe in the medium repressed transcription of both sit and mntH primarily via Fur, although MntR was also involved in this response. Transcriptional control by MntR and Fur was disrupted by site-specific mutations in the putative MntR and Fur binding sites, respectively. Transcription of the sit operon was also affected by the oxygen level and growth phase, but the increased expression observed under high oxygen conditions and higher cell densities is consistent with decreased availability of metals required for repression by the metalloregulatory proteins.

show abstract

supporting

confidence: 67%

mentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional Regulation ofsitABCDofSalmonella entericaSerovar Typhimurium by MntR and Fur

Ikeda¹,

Janakiraman²,

Kehres

et al. 2005

J Bacteriol

Self Cite

112

View full text Add to dashboard Cite

show abstract

“…Allelic variations profoundly affect resistance to Salmonella, Leishmania, and Mycobacteria (32). The Nramp1 protein was initially characterized as a manganese transporter (33), consistent with studies demonstrating that this metal is a virulence factor for certain pathogens, including Yersinia (34) and Salmonella (35). Nramp1 expression is upregulated by cytokines (36), and its function helps to produce nitric oxide along with other pro-inflammatory responses (37,38).…”

mentioning

confidence: 78%

Nramp1 and Other Transporters Involved in Metal Withholding during Infection

Wessling‐Resnick

2015

Journal of Biological Chemistry

112

View full text Add to dashboard Cite

During the course of infection, many natural defenses are set up along the boundaries of the host-pathogen interface. Key among these is the host response to withhold metals to restrict the growth of invading microbes. This simple act of nutritional warfare, starving the invader of an essential element, is an effective means of limiting infection. The physiology of metal withholding is often referred to as "nutritional immunity," and the mechanisms of metal transport that contribute to this host response are the focus of this review.The rationale for host metal withholding against invading pathogens seems intuitive; restriction of any nutrient required for pathogen survival should combat infection. But why metals? The answer to this question becomes crystal clear when one recognizes that iron is required for nearly all life forms, including pathogenic bacteria, with a few rare exceptions that rely on manganese instead (1-7). Iron is essential for ATP production and other metabolic pathways, but its concentration is limited to avoid production of ROS 2 catalyzed by excess levels of this redox-active metal (8). In some organisms, manganese can substitute for redox-active iron to protect against oxidative stress (9, 10). Moreover, most pathogens require manganese to produce their own superoxide dismutase activity to thwart oxidative killing mechanisms exerted by the host (11-13). Iron and manganese have similar ionic radii, have a divalent charge state under physiological conditions, have similar coordination chemistries, and have cellular concentrations in the micromolar range. Consequently, it comes as no surprise that these two metals also share membrane transporters, despite their different cellular functions and distributions. Restriction of iron and/or manganese provides a broad-spectrum metabolic "antidote" against all pathogenic infections, and the common transport pathways used by these metals present selective targets to limit their availability. Although many other immune responses contribute to the fight against infection, metal withholding represents a major force in host defense with combat controlled through transport.The concept of nutritional immunity through metal withholding is largely based on the observations that the iron content of the human diet profoundly affects infectious diseases such as malaria, brucellosis, and tuberculosis (14, 15). Iron overload states such as sickle cell anemia and ␤-thalassemia increase the risk of infection (16 -18). Hereditary hemochromatosis, an inherited disorder of iron metabolism, is also linked to susceptibility to some pathogens (17, 19 -22). Iron deficiency, on the other hand, is associated with decreased survival of individuals infected with HIV and other agents (23). Still, high iron is positively associated with viral load and mortality in HIV (24 -26), suggesting that an optimal balance of iron is necessary. In general terms, low iron status is protective, whereas elevated iron levels promote infection (27, 28). The complexity of host-pathogen interact...

show abstract

“…20,21 The mutation corresponding to the Slc11a1 S allele determines a gly169asp substitution resulting in a nonfunctional protein 22 that promotes an accumulation of ions inside the phagosome that favors pathogen replication. 23 The frequency of the Slc11a1 S allele was 25% in the founder population (F0) of the selection experiment, but shifted to 60% in AIRmin and to 9% in AIRmax after 30 generations of selective breeding. Our results suggest that these frequency changes were the result of selection processes, and implicate this gene, or other closely linked genes, in the control of the acute inflammatory reaction intensity.…”

mentioning

confidence: 99%

Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice

et al. 2006

View full text Add to dashboard Cite

Mice selected for the maximum acute inflammatory reaction (AIRmax) are highly susceptible to pristane-induced arthritis (PIA), whereas mice selected for the minimum response (AIRmin) are resistant. These lines show distinct patterns of leukocyte infiltration and R and S allele frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) gene. In order to study the interactions of the Slc11a1 R and S alleles with the inflammation modulating Quantitative Trait Loci (QTL) during PIA development, homozygous AIRmax RR , AIRmax SS , AIRmin RR and AIRmin SS lines were produced by genotype-assisted breedings. These mice received two intraperitoneal injections of 0.5 ml pristane at 60-day intervals, and the subsequent development of arthritis was assessed for 210 days. Cytokine-secreting cell profiles were investigated using enzyme-linked immunospot. Arthritis incidence in AIRmax RR mice reached 29%, whereas PIA incidence in AIRmax SS mice was 70% by day 180. AIRmin RR mice were resistant, whereas 13.3% of AIRmin SS mice became arthritic. The presence of the defective S allele also increased arthritis severity, although acute inflammation was higher in mice bearing the R allele. A predominant Th0/Th2-type response in Slc11a1 SS mice was observed. These results indicate that Slc11a1 is a strong candidate for the QTL modulating acute inflammation and for PIA.

show abstract

TheSalmonella entericaSerovar Typhimurium Divalent Cation Transport Systems MntH and SitABCD Are Essential for Virulence in anNramp1^G169Murine Typhoid Model

Cited by 114 publications

References 25 publications

Transcriptional Regulation ofsitABCDofSalmonella entericaSerovar Typhimurium by MntR and Fur

Transcriptional Regulation ofsitABCDofSalmonella entericaSerovar Typhimurium by MntR and Fur

Nramp1 and Other Transporters Involved in Metal Withholding during Infection

Slc11a1 (formerly NRAMP1) gene modulates both acute inflammatory reactions and pristane-induced arthritis in mice

Contact Info

Product

Resources

About