Ferric Uptake Regulator-Dependent Antinitrosative Defenses in Salmonella enterica Serovar Typhimurium Pathogenesis

Husain, Maroof; Jones-Carson, Jessica; Liu, Lin; Song, Mi-Ryoung; Saah, J. Royden; Troxell, Bryan; Hassan, Hosni M.; Vázquez‐Torres, Andrés

doi:10.1128/iai.01201-13

Cited by 14 publications

(12 citation statements)

References 42 publications

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“…By virtue of its fast dissociation rate and high affinity for both NO and O 2 , quinol bd oxidase is believed to be at the forefront of NO detoxification under hypoxic conditions. Studies with a fur mutant Salmonella strain have hinted to the importance of NO detoxification by quinol bd oxidases in bacterial pathogenesis [63]. The hypersusceptibility of fur mutant Salmonella to NO generated by iNOS in a murine model of infection is partially dependent on diminished quinol bd oxidase content, perhaps due to a defect in aminolevulinic acid metabolism because the addition of this metabolite restored cytochrome content and resistance to NO.…”

Section: Quinol Oxidases In the Detoxification Of Nomentioning

confidence: 99%

“…The hypersusceptibility of fur mutant Salmonella to NO generated by iNOS in a murine model of infection is partially dependent on diminished quinol bd oxidase content, perhaps due to a defect in aminolevulinic acid metabolism because the addition of this metabolite restored cytochrome content and resistance to NO. In addition to emerging as an important detoxification pathway, nitrosylation of quinol bd oxidases elicits antioxidant defenses in Salmonella by indirectly boosting NADH reducing power [63]. …”

Section: Quinol Oxidases In the Detoxification Of Nomentioning

confidence: 99%

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Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens

Vázquez‐Torres

Bäumler

2016

Current Opinion in Microbiology

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The electrochemical gradient that ensues from the enzymatic activity of cytochromes such as nitrate reductase, nitric oxide reductase, and quinol oxidase contributes to the bioenergetics of the bacterial cell. Reduction of nitrogen oxides by bacterial pathogens can, however, be uncoupled from proton translocation and biosynthesis of ATP or NH4+, but still linked to quinol and NADH oxidation. Ancestral nitric oxide reductases, as well as cytochrome coxidases and quinol bo oxidases evolved from the former, are capable of binding and detoxifying nitric oxide to nitrous oxide. The NO-metabolizing activity associated with these cytochromes can be a sizable source of antinitrosative defense in bacteria during their associations with host cells. Nitrosylation of terminal cytochromes arrests respiration, reprograms bacterial metabolism, stimulates antioxidant defenses and alters antibiotic cytotoxicity. Collectively, the bioenergetics and regulation of redox homeostasis that accompanies the utilization of nitrogen oxides and detoxification of nitric oxide by cytochromes of the electron transport chain increases fitness of many Gram-positive and –negative pathogens during their associations with invertebrate and vertebrate hosts.

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Section: Quinol Oxidases In the Detoxification Of Nomentioning

confidence: 99%

Section: Quinol Oxidases In the Detoxification Of Nomentioning

confidence: 99%

Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens

Vázquez‐Torres

Bäumler

2016

Current Opinion in Microbiology

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“…For example, one of the mechanisms by which Salmonella is resistant to ROS involves a recently discovered efflux pump, which contributes to Salmonella replication in the intestine and in macrophages [66]. Similar to ROS, Salmonella is also susceptible to high concentrations of NO, but possesses mechanisms to defend against moderate levels of nitrosative stress [67–69]. …”

Section: Salmonella Infection In the Intestinementioning

confidence: 99%

Exploiting host immunity: the Salmonella paradigm

Behnsen

Pérez-López

Nuccio

et al. 2015

Trends in Immunology

119

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Pathogens have evolved clever strategies to evade and in some cases exploit the attacks of an activated immune system. Salmonella enterica is one such pathogen, exploiting multiple aspects of host defense to promote its replication in the host. Here we review recent findings on the mechanisms by which Salmonella establishes systemic and chronic infection, including strategies involving manipulation of innate immune signaling and inflammatory forms of cell death, as well as immune evasion by establishing residency in M2 macrophages. We also examine recent evidence showing that the oxidative environment and the high levels of antimicrobial proteins produced in response to localized Salmonella gastrointestinal infection enable the pathogen to successfully outcompete the resident gut microbiota.

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“…For instance, Salmonella is exposed to reactive oxygen species (ROS) produced within the macrophage phagosome (38), and the lack of Fur renders Salmonella highly susceptible to ROS-mediated killing (39). Therefore, the regulatory functions of Fur could protect Salmonella from oxidative stress inside the phagosome (40). In addition, Fur might contribute to Salmonella virulence by controlling expression timing and the expression level of SPI-2 genes.…”

Section: Figmentioning

confidence: 99%

The Iron-Sensing Fur Regulator Controls Expression Timing and Levels of Salmonella Pathogenicity Island 2 Genes in the Course of Environmental Acidification

et al. 2014

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bIn order to survive inside macrophages, Salmonella produces a series of proteins encoded by genes within Salmonella pathogenicity island 2 (SPI-2). In the present study, we report that Fur, a central regulator of iron utilization, negatively controls the expression of SPI-2 genes. Time course analysis of SPI-2 expression after the entry of Salmonella into macrophages revealed that SPI-2 genes are induced earlier and at higher levels in the absence of the Fur regulator. It was hypothesized that Fur repressed the SPI-2 expression that was activated during acidification of the phagosome. Indeed, as pH was lowered from pH 7.0 to pH 5.5, the lack of Fur enabled SPI-2 gene expression to be induced at higher pH and to be expressed at higher levels. Fur controlled SPI-2 genes via repression of the SsrB response regulator, a primary activator of SPI-2 expression. Fur repressed ssrB expression both inside macrophages and under acidic conditions, which we ascribe to the direct binding of Fur to the ssrB promoter. Our study suggests that Salmonella could employ iron inside the phagosome to precisely control the timing and levels of SPI-2 expression inside macrophages.

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Ferric Uptake Regulator-Dependent Antinitrosative Defenses in Salmonella enterica Serovar Typhimurium Pathogenesis

Cited by 14 publications

References 42 publications

Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens

Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens

Exploiting host immunity: the Salmonella paradigm

The Iron-Sensing Fur Regulator Controls Expression Timing and Levels of Salmonella Pathogenicity Island 2 Genes in the Course of Environmental Acidification

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