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Cited by 50Bacterial Genetics and BiotechnologySalmonella and Campylobacter epidemiologyEscherichia coli research studies

Dopamine Is a Siderophore-Like Iron Chelator That Promotes Salmonella enterica Serovar Typhimurium Virulence in Mice

Open access
Dichtl, Stefanie, Demetz, Egon, Haschka, David, Tymoszuk, Piotr, Petzer, Verena, Nairz, Manfred, Seifert, Markus, Hoffmann, Alexander +6 more·2019·mBio
DOI 10.1128/mbio.02624-18PMC PMC6428752
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Abstract

Here we show that dopamine increases bacterial iron incorporation and promotes Salmonella Typhimurium growth both in vitro and in vivo . These observations suggest the potential hazards of pharmacological catecholamine administration in patients with bacterial sepsis but also suggest that the inhibition of bacterial iron acquisition might provide a useful approach to antimicrobial therapy.

AI snapshot

Written from the paper’s full text.

TL;DR

Dopamine acts as a siderophore-like iron chelator that increases iron acquisition by *Salmonella enterica* serovar Typhimurium, promoting bacterial growth in vitro and in mice. This worsens infection outcome and alters host iron homeostasis, suggesting risks of catecholamine use in bacterial sepsis and potential benefit from blocking bacterial iron uptake.

Key findings

  • Dopamine (5 µM) increased S. Typhimurium growth in vitro comparably to 1 µM FeCl₃ and produced an approximately 40% increase in bacterial ⁵⁹Fe acquisition after 3 h; it also increased intramacrophage bacterial numbers in BMDMs.
  • In mice infected i.p. with 500 CFU S. Typhimurium, dopamine treatment (5 mg/kg every 12 h) significantly increased bacterial loads in spleen and liver, increased weight loss and neutrophil numbers, and reduced survival, with dopamine-treated mice succumbing approximately 12 h earlier than solvent-treated mice.
  • Dopamine lowered serum iron and transferrin saturation, increased serum hepcidin, and reduced Fpn1⁺ CD45⁺ cells and Fpn1 protein in spleen/liver; circulating Salmonella numbers were significantly higher in dopamine-treated mice.
  • Dopamine’s growth-promoting effect required bacterial iron uptake systems and QseC: it failed to stimulate growth of an entC/sit/feo triple mutant or a qseC mutant, and single entC, feo, or sitABCD mutants no longer showed a significant dopamine-induced increase in vivo, with SitABCD suggested as principally involved.

Methods

  • In vitro: S. Typhimurium ATCC 14028 was grown with 5 µM dopamine, 1 µM FeCl₃, or solvent; BMDMs from C57BL/6 mice were infected at MOI 10 (or MOI 20 for iron acquisition), treated with dopamine ± tranylcypromine, and assessed by CFU plating, ⁵⁹Fe counting, qRT-PCR, Western blot, and flow cytometry.
  • In vivo: male C57BL/6N mice aged 8–10 weeks were infected i.p. with 500 CFU wild-type S. Typhimurium or mutants (5,000 CFU for entC, feo, or sitABCD mutants), injected i.p. with 5 mg/kg dopamine or PBS every 12 h, and sacrificed after 72 h; survival was monitored, and LED209 was given orally at 20 mg/kg.
  • Statistics: unpaired two-tailed Student’s t test or Mann-Whitney test for two groups, ANOVA with Bonferroni correction for multiple comparisons, and log-rank test for survival; P < 0.05 was considered significant.

Limitations

  • The paper does not include a dedicated limitations section.
  • Evident from the text: findings are limited to mouse and BMDM models, with no human clinical data; the i.p. infection model may not represent all clinical Salmonella disease presentations.
  • Some in vivo mutant effects were trends rather than significant (e.g., entC/feo mutants and qseC mutant bacterial loads), and the authors note QseC has complex, variable influence on iron-regulated genes, so mechanistic conclusions are partly inferential.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1128/mbio.02624-18

Cites

59 of 59 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 40 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Decreased expression of sitB was observed in qseC mutant S. Typhimurium in comparison to Wt.

    “decreased expression of sitB was observed in qseC mutant S. Typhimurium in comparison to Wt”
    Quote in the paperSubstantial claim
  • Findingown data

    Serum iron concentrations were significantly decreased in infected mice receiving DA.

    “Serum iron concentrations were significantly decreased in infected mice receiving DA”
    Quote in the paperSubstantial claim
  • Findingown data

    Addition of DA resulted in significantly increased intramacrophage numbers of S. Typhimurium compared to infected macrophages without added DA.

    “The addition of DA resulted in significantly increased intramacrophage numbers of S. Typhimurium in comparison to infected macrophages without added DA serving as a control”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Tranylcypromine alone has no effect on bacterial numbers compared to controls.
  • Findingown data

    DA-treated mice had significantly enhanced numbers of neutrophils.

    “significantly enhanced numbers of neutrophils (Fig. 2D)”
    Quote in the paperNot a substantial claim
  • Findingown data

    Circulating levels of TNF-α were significantly increased in infected mice receiving DA.

    “circulating levels of the cytokine TNF-α were actually significantly increased in infected mice receiving DA”
    Quote in the paperNot a substantial claim
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 16

  • May combine two claims.

    Findingown data

    Dopamine promotes Salmonella Typhimurium growth both in vitro and in vivo.

    “promotes Salmonella Typhimurium growth both in vitro and in vivo”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    We could not detect a DA-dependent increase in serum hepcidin concentrations in mice infected with the S. Typhimurium qseC mutant, nor in Wt S. Typhimurium-infected mice receiving LED209.

    “we could not detect a DA-dependent increase in serum hepcidin concentrations in mice infected with the S. Typhimurium qseC mutant, nor in Wt S. Typhimurium-infected mice receiving the pharmacological QseC inhibitor LED209”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Mice receiving DA exhibited significantly reduced survival and succumbed to infection approximately 12 h earlier than solvent-treated mice.

    “Mice receiving DA exhibited significantly reduced survival and succumbed to infection approximately 12 h earlier than solvent-treated mice.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    fepC and fur expression are QseC independent.

    “fepC (Fig. S1G) and fur (Fig. S1F) expression are QseC independent”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Although DA administration resulted in increased bacterial numbers in all three groups, bacterial loads were lower by trend in mice infected with the qseC mutant compared with Wt S. Typhimurium.

    “although DA administration resulted in increased bacterial numbers in all three groups, bacterial loads were lower by trend in mice infected with the qseC mutant compared with Wt S. Typhimurium”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Infection of mice with Wt S. Typhimurium in the presence or absence of LED209 did not result in different bacterial numbers, which was also observed in mice infected with an S. Typhimurium qseC mutant strain.

    “Infection of mice with Wt S. Typhimurium in the presence or absence of LED209 did not result in different bacterial numbers, which was also observed in mice infected with an S. Typhimurium qseC mutant strain.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DA treatment caused increased bacterial load in spleens in both Wt and Lcn2−/− mice, but no significant difference in bacterial numbers was observed between Wt and Lcn2−/− mice.

    “DA treatment caused an increased bacterial load in the spleens in both groups, but no significant difference in bacterial numbers was observed between Wt and Lcn2−/− mice”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Upon infection with S. Typhimurium, transferrin saturation declined significantly, and DA treatment led to a further decrease in transferrin saturation.

    “Upon infection with S. Typhimurium, transferrin saturation declined significantly, and DA treatment led to a further decrease in transferrin saturation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Hepcidin levels increased in S. Typhimurium-infected solvent-treated mice, and DA administration resulted in a further increase in serum hepcidin levels.

    “hepcidin levels increased in S. Typhimurium-infected solvent-treated mice (Fig. 3F), and DA administration resulted in a further increase in serum hepcidin levels.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DA administration resulted in decreased Fpn1 expression in Wt S. Typhimurium-infected mice, but this was not observed in mice infected with qseC mutant S. Typhimurium or in mice receiving LED209.

    “DA administration resulted in decreased Fpn1 expression in Wt S. Typhimurium-infected mice. However, this was not observed in mice infected with qseC mutant S. Typhimurium or in mice receiving LED209”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A trend toward higher bacterial burdens was still observed in DA-treated mice infected with entC or feo mutant Salmonella but not in DA-treated mice infected with sitABCD mutant Salmonella.

    “Nevertheless, a trend toward higher bacterial burdens was still observed in DA-treated mice infected with entC or feo mutant Salmonella but not in DA-treated mice infected with sitABCD mutant Salmonella.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    After infection, the percentage of Fpn1+ splenocytes further declined, and DA treatment led to a further decrease in splenic Fpn1+ CD45+ cells.

    “After infection, the percentage of Fpn1+ splenocytes further declined, and DA treatment led to a further decrease in splenic Fpn1+ CD45+ cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Dopamine stimulates proliferation and intramacrophage survival of Salmonella Typhimurium.

    “Here, we provide novel evidence that the catecholamine DA stimulates the proliferation and intramacrophage survival of Salmonella enterica serovar Typhimurium”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    DA effects on the ferroportin-hepcidin axis can increase iron availability for intramacrophage bacteria, which may contribute to the influence of DA on bacterial burden.

    “This may contribute to the influence of DA on bacterial burden, as DA effects on the ferroportin-hepcidin axis can increase iron availability for intramacrophage bacteria.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Salmonella has both siderophore-dependent and -independent strategies to acquire iron from the host.

    “Salmonella has both siderophore-dependent and -independent strategies to acquire iron from the host (14).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [14] Sassone-Corsi M, Chairatana P, Zheng T, Perez-Lopez A, Edwards RA, George MD, Nolan EM, Raffatellu M 2016 Siderophore-based immunization strategy to inhibit growth of enteric pathogens. Proc Natl Acad Sci U S A 113: 13462– 13467. doi: 10.1073/pnas.1606290113. 27821741 PMC5127304 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Dopamine impacts the iron homeostasis of macrophages, promoting cellular iron accumulation in macrophages and stimulating intracellular antistress responses.

    “We have recently shown that the catecholamine dopamine (DA) impacts the iron homeostasis of macrophages, promoting cellular iron accumulation in macrophages by a poorly understood mechanism and stimulating intracellular antistress responses (20).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Dichtl S, Haschka D, Nairz M, Seifert M, Volani C, Lutz O, Weiss G 2018 Dopamine promotes cellular iron accumulation and oxidative stress responses in macrophages. Biochem Pharmacol 148: 193– 201. doi: 10.1016/j.bcp.2017.12.001. 29208364 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Other catechols can serve as pseudosiderophores that promote bacterial growth under iron-restricted conditions.

    “In addition to bacterium-derived siderophores like enterobactin, other catechols can serve as pseudosiderophores that are able to promote bacterial growth under iron-restricted conditions (18).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Miethke M, Skerra A 2010 Neutrophil gelatinase-associated lipocalin expresses antimicrobial activity by interfering with L-norepinephrine-mediated bacterial iron acquisition. Antimicrob Agents Chemother 54: 1580– 1589. doi: 10.1128/AAC.01158-09. 20086155 PMC2849382 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Salmonella synthesizes catecholate-type siderophores such as enterochelin and salmochelin, a C-glucosylated enterobactin, to capture and internalize ferric iron via siderophore receptors.

    “Salmonella synthesizes catecholate-type siderophores such as enterochelin and salmochelin, a C-glucosylated enterobactin, to capture and internalize ferric iron via siderophore receptors (15–17).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [15] Baumler AJ, Norris TL, Lasco T, Voight W, Reissbrodt R, Rabsch W, Heffron F 1998 IroN, a novel outer membrane siderophore receptor characteristic of Salmonella enterica. J Bacteriol 180: 1446– 1453. 9515912 PMC107043 source

      Not checked in the free run.

    • cites [16] Rabsch W, Methner U, Voigt W, Tschape H, Reissbrodt R, Williams PH 2003 Role of receptor proteins for enterobactin and 2,3-dihydroxybenzoylserine in virulence of Salmonella enterica. Infect Immun 71: 6953– 6961. 14638784 PMC308886 source

      Not checked in the free run.

    • cites [17] Fischbach MA, Lin H, Liu DR, Walsh CT 2005 In vitro characterization of IroB, a pathogen-associated C-glycosyltransferase. Proc Natl Acad Sci U S A 102: 571– 576. doi: 10.1073/pnas.0408463102. 15598734 PMC545562 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    All animal experiments were performed according to institutional and governmental guidelines and the design was approved by the Austrian Federal Ministry of Science and Research.

    “All animal experiments were performed according to institutional and governmental guidelines in the animal facility of the Medical University of Innsbruck. Design of the animal experiments was approved by the Austrian Federal Ministry of Science and Research (BMWF-66.011/0092-II/3b/2013).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    LED209 is a small molecule inhibitor of QseC.

    “In various pathogens, a small molecule inhibitor of QseC called LED209 was described (28, 29).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [28] Yang Q, Anh ND, Bossier P, Defoirdt T 2014 Norepinephrine and dopamine increase motility, biofilm formation, and virulence of Vibrio harveyi. Front Microbiol 5: 584. doi: 10.3389/fmicb.2014.00584. 25414697 PMC4222227 source

      Not checked in the free run.

    • cites [29] Moreira CG, Sperandio V 2012 Interplay between the QseC and QseE bacterial adrenergic sensor kinases in Salmonella enterica serovar Typhimurium pathogenesis. Infect Immun 80: 4344– 4353. doi: 10.1128/IAI.00803-12. 23027532 PMC3497441 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fpn1 overexpression improves control of the replication of intracellular bacteria, including Salmonella.

    “Fpn1 overexpression has been shown to improve control of the replication of intracellular bacteria, including Salmonella (38–40).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [38] Nairz M, Theurl I, Ludwiczek S, Theurl M, Mair SM, Fritsche G, Weiss G 2007 The co-ordinated regulation of iron homeostasis in murine macrophages limits the availability of iron for intracellular Salmonella typhimurium. Cell Microbiol 9: 2126– 2140. doi: 10.1111/j.1462-5822.2007.00942.x. 17466014 source

      Not checked in the free run.

    • cites [39] Paradkar PN, De Domenico I, Durchfort N, Zohn I, Kaplan J, Ward DM 2008 Iron depletion limits intracellular bacterial growth in macrophages. Blood 112: 866– 874. doi: 10.1182/blood-2007-12-126854. 18369153 PMC2481528 source

      Not checked in the free run.

    • cites [40] Nairz M, Schleicher U, Schroll A, Sonnweber T, Theurl I, Ludwiczek S, Talasz H, Brandacher G, Moser PL, Muckenthaler MU, Fang FC, Bogdan C, Weiss G 2013 Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection. J Exp Med 210: 855– 873. doi: 10.1084/jem.20121946. 23630227 PMC3646493 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Dopamine is a neurotransmitter in the catechol family and is often used as a first-line vasoactive drug in patients with septic shock.

    “Dopamine (DA) is a neurotransmitter in the catechol family, which is often used as first-line vasoactive drug in patients with septic shock (43).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, Brasseur A, Defrance P, Gottignies P, Vincent JL, SOAP II Investigators. 2010 Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 362: 779– 789. doi: 10.1056/NEJMoa0907118. 20200382 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Fpn1 is the only known cellular iron exporter and a target of hepcidin, which promotes Fpn1 internalization and the inhibition of cellular iron egress.

    “Fpn1 is the only known cellular iron exporter and a target of hepcidin, which promotes Fpn1 internalization and the inhibition of cellular iron egress (36, 37).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [36] Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J 2004 Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306: 2090– 2093. doi: 10.1126/science.1104742. 15514116 source

      Not checked in the free run.

    • cites [37] Sebastiani G, Wilkinson N, Pantopoulos K 2016 Pharmacological targeting of the hepcidin/ferroportin axis. Front Pharmacol 7: 160. doi: 10.3389/fphar.2016.00160. 27445804 PMC4914558 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    QseC regulates the transcription of Salmonella pathogenicity island 1 (SPI-1) genes, the SPI-2 effector locus sifA, and flagellar genes, both in vivo and in vitro.

    “QseC regulates the transcription of Salmonella pathogenicity island 1 (SPI-1) genes, the SPI-2 effector locus sifA, and flagellar genes, both in vivo and in vitro (26, 27).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] Moreira CG, Weinshenker D, Sperandio V 2010 QseC mediates Salmonella enterica serovar Typhimurium virulence in vitro and in vivo. Infect Immun 78: 914– 926. doi: 10.1128/IAI.01038-09. 20028809 PMC2825943 source

      Not checked in the free run.

    • cites [27] LaRock DL, Chaudhary A, Miller SI 2015 Salmonellae interactions with host processes. Nat Rev Microbiol 13: 191– 205. doi: 10.1038/nrmicro3420. 25749450 PMC5074537 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SitABCD mediates the uptake of ferrous iron and manganese.

    “the ATP-binding cassette transporter SitABCD mediates the uptake of ferrous iron and manganese (31–34)”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [31] Karlinsey JE, Maguire ME, Becker LA, Crouch ML, Fang FC 2010 The phage shock protein PspA facilitates divalent metal transport and is required for virulence of Salmonella enterica sv. Typhimurium. Mol Microbiol 78: 669– 685. doi: 10.1111/j.1365-2958.2010.07357.x. 20807201 PMC2963695 source

      Not checked in the free run.

    • cites [32] Kehres DG, Janakiraman A, Slauch JM, Maguire ME 2002 SitABCD is the alkaline Mn(2+) transporter of Salmonella enterica serovar Typhimurium. J Bacteriol 184: 3159– 3166. 12029031 PMC135093 source

      Not checked in the free run.

    • cites [33] Kehres DG, Zaharik ML, Finlay BB, Maguire ME 2000 The NRAMP proteins of Salmonella typhimurium and Escherichia coli are selective manganese transporters involved in the response to reactive oxygen. Mol Microbiol 36: 1085– 1100. 10844693 source

      Not checked in the free run.

    • cites [34] Zhou D, Hardt WD, Galan JE 1999 Salmonella typhimurium encodes a putative iron transport system within the centisome 63 pathogenicity island. Infect Immun 67: 1974– 1981. 10085045 PMC96555 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    FeoAB system transports ferrous iron.

    “the FeoAB system transports ferrous iron (35)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [35] Braun V 2005 Bacterial iron transport related to virulence. Contrib Microbiol 12: 210– 233. doi: 10.1159/000081697. 15496782 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Catecholamines can promote the growth of various pathogenic bacteria, including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Yersinia enterocolitica, and Salmonella enterica.

    “previous studies have shown that catecholamines can promote the growth of various pathogenic bacteria, including Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Yersinia enterocolitica, and Salmonella enterica (21–23).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [21] Beasley FC, Marolda CL, Cheung J, Buac S, Heinrichs DE 2011 Staphylococcus aureus transporters Hts, Sir, and Sst capture iron liberated from human transferrin by staphyloferrin A, staphyloferrin B, and catecholamine stress hormones, respectively, and contribute to virulence. Infect Immun 79: 2345– 2355. doi: 10.1128/IAI.00117-11. 21402762 PMC3125851 source

      Not checked in the free run.

    • cites [22] Freestone PP, Haigh RD, Lyte M 2007 Specificity of catecholamine-induced growth in Escherichia coli O157:H7, Salmonella enterica and Yersinia enterocolitica. FEMS Microbiol Lett 269: 221– 228. doi: 10.1111/j.1574-6968.2006.00619.x. 17229058 source

      Not checked in the free run.

    • cites [23] Coulanges V, Andre P, Ziegler O, Buchheit L, Vidon DJ 1997 Utilization of iron-catecholamine complexes involving ferric reductase activity in Listeria monocytogenes. Infect Immun 65: 2778– 2785. 9199450 PMC175392 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The prodrug LED209 does not interfere with pathogen growth and may therefore exert less evolutionary pressure favoring the development of drug resistance.

    “The prodrug LED209 does not interfere with pathogen growth and may therefore exert less evolutionary pressure favoring the development of drug resistance (30).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Curtis MM, Russell R, Moreira CG, Adebesin AM, Wang C, Williams NS, Taussig R, Stewart D, Zimmern P, Lu B, Prasad RN, Zhu C, Rasko DA, Huntley JF, Falck JR, Sperandio V 2014 QseC inhibitors as an antivirulence approach for Gram-negative pathogens. mBio 5: e02165-14. doi: 10.1128/mBio.02165-14. 25389178 PMC4235214 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Catecholamines can bind to two histidine sensor kinases QseC and QseE, resulting in effects on bacterial proliferation and virulence.

    “catecholamines can also bind to two histidine sensor kinases QseC and QseE, resulting in effects on bacterial proliferation and virulence (24).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Hughes DT, Clarke MB, Yamamoto K, Rasko DA, Sperandio V 2009 The QseC adrenergic signaling cascade in enterohemorrhagic E. coli (EHEC). PLoS Pathog 5: e1000553. doi: 10.1371/journal.ppat.1000553. 19696934 PMC2726761 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    QseC acts upstream of QseE.

    “The transcription of qseE is activated by QseC; therefore, QseC acts upstream of QseE (25).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Reading NC, Torres AG, Kendall MM, Hughes DT, Yamamoto K, Sperandio V 2007 A novel two-component signaling system that activates transcription of an enterohemorrhagic Escherichia coli effector involved in remodeling of host actin. J Bacteriol 189: 2468– 2476. doi: 10.1128/JB.01848-06. 17220220 PMC1899401 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Clinically relevant concentrations of DA can compromise the iron-binding integrity of Tf and thereby enable proliferation of invading bacteria by making serum less bacteriostatic.

    “Sandrini et al. found that clinically relevant concentrations of DA can compromise the iron-binding integrity of Tf and thereby enable proliferation of invading bacteria by making serum less bacteriostatic (19).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [19] Sandrini SM, Shergill R, Woodward J, Muralikuttan R, Haigh RD, Lyte M, Freestone PP 2010 Elucidation of the mechanism by which catecholamine stress hormones liberate iron from the innate immune defense proteins transferrin and lactoferrin. J Bacteriol 192: 587– 594. doi: 10.1128/JB.01028-09. 19820086 PMC2805316 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Salmonella may contribute to hepcidin induction, possibly via stimulation of estrogen-related receptor γ signaling in the liver.

    “Interestingly, the deletion of QseC blunted this hepcidin-inducing effect, suggesting that Salmonella may contribute to hepcidin induction, possibly via stimulation of estrogen-related receptor γ signaling in the liver (46).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Kim DK, Jeong JH, Lee JM, Kim KS, Park SH, Kim YD, Koh M, Shin M, Jung YS, Kim HS, Lee TH, Oh BC, Kim JI, Park HT, Jeong WI, Lee CH, Park SB, Min JJ, Jung SI, Choi SY, Choy HE, Choi HS 2014 Inverse agonist of estrogen-related receptor gamma controls Salmonella typhimurium infection by modulating host iron homeostasis. Nat Med 20: 419– 424. doi: 10.1038/nm.3483. 24658075 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Dopamine promotes Salmonella bacterial growth by at least two mechanisms, both of which increase bacterial iron availability.

    “DA appears to promote bacterial growth by at least two mechanisms, both of which increase bacterial iron availability.”
    Quote in the paperSubstantial claim
33 of 33

  • The paper relies on this without support.

    Tranylcypromine alone has no effect on bacterial numbers compared to controls.

    “The addition of tranylcypromine without DA had no effect on bacterial numbers compared to controls (results not shown).”

  • The paper relies on this without support.

    The mouse model of Salmonella infection and dopamine treatment is representative of human septic shock patients.

    “Our findings suggest that the use of DA as a vasoactive drug in patients with septic shock due to infection with intracellular pathogens such as Salmonella might have adventitious effects on iron homeostasis and bacterial growth that are detrimental to the host.”

  • The paper relies on this without support.

    The dopamine doses and concentrations used in mice and in vitro are comparable to those in patients.

    “Mice were injected i.p. with 5 mg DA/kg of body weight dissolved in 200 µl PBS or an equal volume of PBS every 12 h and sacrificed after 72 h of infection (52).”
3 of 3

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  • Host-derived catechols such as dopamine may be used by bacteria as an iron cargo to stimulate bacterial proliferation, thereby negatively impacting the outcome of such infections.

    “host derived catechols such as dopamine may be used by bacteria as an iron cargo to stimulate bacterial proliferation thereby negatively impacting on the outcome of such infections”

    From Iron in immune cell function and host defense (2021) · cites this paper as [46]

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Authors
Dichtl, S., Demetz, E., Haschka, D., Tymoszuk, P., Petzer, V., Nairz, M., Seifert, M., Hoffmann, A., Brigo, N., Würzner, R., Theurl, I., Karlinsey, J. E., Fang, F. C., & Weiss, G.
Affiliations
  • Innsbruck Medical University (AT)
  • University of Washington (US)
Corresponding author
Weiss, Günter
ORCID
Venue
mBio
Publisher
American Society for Microbiology
Published
2019-02-26
Volume
10
Issue
1
ISSN
  • 2150-7511 (ISSN-L)
  • 2161-2129
DOI
10.1128/mbio.02624-18
PMC
PMC6428752
OpenAlex
W2914031632
Semantic Scholar
4ef4882f3a056d0c356e88266a1906e18caf8b66
Cited by
50
References
60
Citations by year
2026: 9 · 2025: 5 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 11 · 2020: 6 · 2019: 2
FWCI
3.46
Type
journal article
Language
en
Open access
Licence
Locations
  • mBio (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • HHS | National Institutes of Health (AI 112640)
  • Austrian Science Fund (W1253)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
Keywords
dopamine, Salmonella typhimurium, bacterial iron acquisition, bacterial virulence, catecholamines, bacterial sepsis, iron incorporation, antimicrobial therapy
MeSH terms
Animals, Cells, Cultured, Chelating Agents, Disease Models, Animal, Dopamine, Iron, Liver, Macrophages, Mice, Inbred C57BL, Salmonella Infections, Salmonella typhimurium, Spleen, Virulence, Survival Analysis, Siderophores, Bacterial Load

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-07.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-07.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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