An overview of<i>Salmonella enterica</i>metal homeostasis pathways during infection

Cunrath, Olivier; Palmer, Jacob D

doi:10.1093/femsml/uqab001

Cited by 12 publications

(10 citation statements)

References 223 publications

(301 reference statements)

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“…MntH, a proton-dependent NRAMP1 homolog, actively imports Mn 2+ with a K m of 0.1 μM ( Kehres et al, 2000 ). Salmonella upregulate MntH expression in response to both low Mn 2+ concentrations and oxidative stress ( Kehres et al, 2002a ; Cunrath and Palmer, 2021 ). MntH mutant Salmonella grow poorly in mouse macrophages, but replicate rather well in mice ( Boyer et al, 2002 ; Zaharik et al, 2004 ; Diaz-Ochoa et al, 2016 ).…”

Section: Mn 2+ Import Promotes Salmonell...mentioning

confidence: 99%

Manganese Utilization in Salmonella Pathogenesis: Beyond the Canonical Antioxidant Response

Uppalapati

Vázquez‐Torres

2022

Front. Cell Dev. Biol.

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The metal ion manganese (Mn2+) is equally coveted by hosts and bacterial pathogens. The host restricts Mn2+ in the gastrointestinal tract and Salmonella-containing vacuoles, as part of a process generally known as nutritional immunity. Salmonella enterica serovar Typhimurium counteract Mn2+ limitation using a plethora of metal importers, whose expression is under elaborate transcriptional and posttranscriptional control. Mn2+ serves as cofactor for a variety of enzymes involved in antioxidant defense or central metabolism. Because of its thermodynamic stability and low reactivity, bacterial pathogens may favor Mn2+-cofactored metalloenzymes during periods of oxidative stress. This divalent metal catalyzes metabolic flow through lower glycolysis, reductive tricarboxylic acid and the pentose phosphate pathway, thereby providing energetic, redox and biosynthetic outputs associated with the resistance of Salmonella to reactive oxygen species generated in the respiratory burst of professional phagocytic cells. Combined, the oxyradical-detoxifying properties of Mn2+ together with the ability of this divalent metal cation to support central metabolism help Salmonella colonize the mammalian gut and establish systemic infections.

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Section: Mn 2+ Import Promotes Salmonell...mentioning

confidence: 99%

Manganese Utilization in Salmonella Pathogenesis: Beyond the Canonical Antioxidant Response

Uppalapati

Vázquez‐Torres

2022

Front. Cell Dev. Biol.

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“…Most bacteria require trace metals such as iron, cobalt, and zinc for growth and metabolism and must scavenge these metals from their environment (Cunrath & Palmer, 2021 ; Ratledge & Dover, 2000 ). Iron in particular is an essential micronutrient required for diverse biochemical processes in the bacterial cell and plays a significant role as a cofactor in various enzymatic reactions (Ratledge & Dover, 2000 ).…”

Section: Introductionmentioning

confidence: 99%

“…Salmonella enterica serovar Typhimurium ( S . Typhimurium), the subject of this study, produces and secretes two catechol siderophores—enterobactin (enterochelin) and salmochelin, a C‐glucosylated form of enterobactin—when exposed to low‐iron conditions (Cunrath & Palmer, 2021 ; Mey et al, 2021 ; Pollack & Neilands, 1970 ). Salmonella also has the capacity to pirate siderophores produced by fungi or other bacteria, known as xenosiderophores or exosiderophores.…”

Section: Introductionmentioning

confidence: 99%

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FoxR is an AraC‐like transcriptional regulator of ferrioxamine uptake in Salmonella enterica

Saldaña-Ahuactzi

Knodler

2022

Molecular Microbiology

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Salmonella enterica spp. produce siderophores to bind iron with high affinity and can also use three xenosiderophores secreted by other microorganisms, ferrichrome, coprogen, and ferrioxamine. Here we focused on FoxA, a TonB‐dependent transporter of ferrioxamines. Adjacent to foxA is a gene annotated as a helix‐turn‐helix (HTH) domain‐containing protein, SL0358 (foxR), in the Salmonella enterica serovar Typhimurium SL1344 genome. FoxR shares homology with transcriptional regulators belonging to the AraC/XylS family. foxR is syntenic with foxA in the Enterobacteriaceae family, suggesting their functional relatedness. Both foxA and foxR are repressed by the ferric uptake regulator (Fur) under iron‐rich growth conditions. When iron is scarce, FoxR acts as a transcriptional activator of foxA by directly binding to its upstream regulatory region. A point mutation in the HTH domain of FoxR abolished this binding, as did mutation of a direct repeat motif in the foxA upstream regulatory region. Desferrioxamine (DFOE) enhanced FoxR protein stability and foxA transcription but did not affect the affinity of FoxR binding to the foxA regulatory region. In summary, we have identified FoxR as a new member of the AraC/XylS family that regulates xenosiderophore‐mediated iron uptake by S. Typhimurium and likely other Enterobacteriaceae members.

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“…Nutritional immunity is a powerful strategy at the core of the battle between host survival and pathogen proliferation. A host can prevent pathogen theft by sequestering essential nutrients, such as Mg, Fe, and Zn, or actively intoxicating pathogens with resource overload (Abu Kwaik and Bumann, 2013; Cunrath and Palmer, 2021), a phenomenon known as nutritional immunology or immunometabolism (Cotter et al, 2019; Pålsson-McDermott and O’Neill, 2020). Nutritional immunology frequently involves either an increase or decrease in food intake.…”

Section: Introductionmentioning

confidence: 99%

Natural variation in host defense strategies impacts both host and pathogen fitness

Pfenning-Butterworth

Vetter

Hite

2022

Preprint

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1. Animals ranging from mosquitoes to humans often vary their feeding behavior when infected or merely exposed to pathogens. For example, some individuals drastically reduce their food intake ('illness-mediated anorexia') while others increase food intake ('hyperphagia'). While these so-called 'sickness behaviors' are well documented, their functional consequences remain poorly resolved. 2. Here, we examine links between natural genetic variation in susceptibility to infection, feeding behaviors, multiple traits of the host, and within-host pathogen production. Using a zooplankton host (Daphnia dentifera) and a fungal pathogen (Metschnikowia bicuspidata) as a case study, we show that genotypic and dose-dependent variation in feeding behaviors are associated with both resistance and tolerance mechanisms. 3. In one genotype, immune-mediated anorexia was associated with increased tolerance to infection; unlike other genotypes, these individuals did not upregulate phenoloxidase activity, but lived longer, had the highest overall fecundity, and produced higher pathogen loads, despite their reduced growth rates and resultant smaller body sizes. In these hosts, peak parasite load remained unchanged, suggesting a tolerance mechanism that offset fecundity costs. 4. In other genotypes, feeding behaviors followed either a flat or hump-shaped pattern with pathogen dose, exhibiting hyperphagia at intermediate doses and anorexia at higher doses. In these cases, anorexia functioned primarily in resistance. 5. Our results suggest that infection-mediated changes in host feeding behavior — which are traditionally interpreted as immunopathology — may in fact serve as crucial components of host defense strategies. Moreover, these phenomena vary across host genotypes, and were associated with apparent trade-offs with another melanization component of immune defense. Together, these results underscore that while resistance and tolerance are typically viewed as alternative and fixed defense strategies, the immense genetic diversity for immune defense may result in more of a plastic spectrum spanning a gradient from resistance to tolerance.

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An overview ofSalmonella entericametal homeostasis pathways during infection

Cited by 12 publications

References 223 publications

Manganese Utilization in Salmonella Pathogenesis: Beyond the Canonical Antioxidant Response

Manganese Utilization in Salmonella Pathogenesis: Beyond the Canonical Antioxidant Response

FoxR is an AraC‐like transcriptional regulator of ferrioxamine uptake in Salmonella enterica

Natural variation in host defense strategies impacts both host and pathogen fitness

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