Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice
ABSTRACT We have recently shown that the catecholamine dopamine regulates cellular iron homeostasis in macrophages. As iron is an essential nutrient for microbes, and intracellular iron availability affects the growth of intracellular bacteria, we studied whether dopamine administration impacts the...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-02-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02624-18 |
| _version_ | 1818826059938791424 |
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| author | Stefanie Dichtl Egon Demetz David Haschka Piotr Tymoszuk Verena Petzer Manfred Nairz Markus Seifert Alexander Hoffmann Natascha Brigo Reinhard Würzner Igor Theurl Joyce E. Karlinsey Ferric C. Fang Günter Weiss |
| author_facet | Stefanie Dichtl Egon Demetz David Haschka Piotr Tymoszuk Verena Petzer Manfred Nairz Markus Seifert Alexander Hoffmann Natascha Brigo Reinhard Würzner Igor Theurl Joyce E. Karlinsey Ferric C. Fang Günter Weiss |
| author_sort | Stefanie Dichtl |
| collection | DOAJ |
| description | ABSTRACT We have recently shown that the catecholamine dopamine regulates cellular iron homeostasis in macrophages. As iron is an essential nutrient for microbes, and intracellular iron availability affects the growth of intracellular bacteria, we studied whether dopamine administration impacts the course of Salmonella infections. Dopamine was found to promote the growth of Salmonella both in culture and within bone marrow-derived macrophages, which was dependent on increased bacterial iron acquisition. Dopamine administration to mice infected with Salmonella enterica serovar Typhimurium resulted in significantly increased bacterial burdens in liver and spleen, as well as reduced survival. The promotion of bacterial growth by dopamine was independent of the siderophore-binding host peptide lipocalin-2. Rather, dopamine enhancement of iron uptake requires both the histidine sensor kinase QseC and bacterial iron transporters, in particular SitABCD, and may also involve the increased expression of bacterial iron uptake genes. Deletion or pharmacological blockade of QseC reduced but did not abolish the growth-promoting effects of dopamine. Dopamine also modulated systemic iron homeostasis by increasing hepcidin expression and depleting macrophages of the iron exporter ferroportin, which enhanced intracellular bacterial growth. Salmonella lacking all central iron uptake pathways failed to benefit from dopamine treatment. These observations are potentially relevant to critically ill patients, in whom the pharmacological administration of catecholamines to improve circulatory performance may exacerbate the course of infection with siderophilic bacteria. IMPORTANCE 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. |
| first_indexed | 2024-12-19T00:21:39Z |
| format | Article |
| id | doaj.art-57f584f7f41d47c996f27ad5c95554b5 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T00:21:39Z |
| publishDate | 2019-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-57f584f7f41d47c996f27ad5c95554b52022-12-21T20:45:32ZengAmerican Society for MicrobiologymBio2150-75112019-02-0110110.1128/mBio.02624-18Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in MiceStefanie Dichtl0Egon Demetz1David Haschka2Piotr Tymoszuk3Verena Petzer4Manfred Nairz5Markus Seifert6Alexander Hoffmann7Natascha Brigo8Reinhard Würzner9Igor Theurl10Joyce E. Karlinsey11Ferric C. Fang12Günter Weiss13Department of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDivision of Microbiology and Hygiene, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaDepartment of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, USADepartment of Laboratory Medicine, University of Washington School of Medicine, Seattle, Washington, USADepartment of Internal Medicine II (Infectious Diseases, Immunology, Rheumatology and Pneumology), Medical University of Innsbruck, Innsbruck, AustriaABSTRACT We have recently shown that the catecholamine dopamine regulates cellular iron homeostasis in macrophages. As iron is an essential nutrient for microbes, and intracellular iron availability affects the growth of intracellular bacteria, we studied whether dopamine administration impacts the course of Salmonella infections. Dopamine was found to promote the growth of Salmonella both in culture and within bone marrow-derived macrophages, which was dependent on increased bacterial iron acquisition. Dopamine administration to mice infected with Salmonella enterica serovar Typhimurium resulted in significantly increased bacterial burdens in liver and spleen, as well as reduced survival. The promotion of bacterial growth by dopamine was independent of the siderophore-binding host peptide lipocalin-2. Rather, dopamine enhancement of iron uptake requires both the histidine sensor kinase QseC and bacterial iron transporters, in particular SitABCD, and may also involve the increased expression of bacterial iron uptake genes. Deletion or pharmacological blockade of QseC reduced but did not abolish the growth-promoting effects of dopamine. Dopamine also modulated systemic iron homeostasis by increasing hepcidin expression and depleting macrophages of the iron exporter ferroportin, which enhanced intracellular bacterial growth. Salmonella lacking all central iron uptake pathways failed to benefit from dopamine treatment. These observations are potentially relevant to critically ill patients, in whom the pharmacological administration of catecholamines to improve circulatory performance may exacerbate the course of infection with siderophilic bacteria. IMPORTANCE 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.https://journals.asm.org/doi/10.1128/mBio.02624-18Salmonella TyphimuriumcatecholaminedopamineironqseCsepsis |
| spellingShingle | Stefanie Dichtl Egon Demetz David Haschka Piotr Tymoszuk Verena Petzer Manfred Nairz Markus Seifert Alexander Hoffmann Natascha Brigo Reinhard Würzner Igor Theurl Joyce E. Karlinsey Ferric C. Fang Günter Weiss Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice mBio Salmonella Typhimurium catecholamine dopamine iron qseC sepsis |
| title | Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice |
| title_full | Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice |
| title_fullStr | Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice |
| title_full_unstemmed | Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice |
| title_short | Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice |
| title_sort | dopamine is a siderophore like iron chelator that promotes italic toggle yes salmonella enterica italic serovar typhimurium virulence in mice |
| topic | Salmonella Typhimurium catecholamine dopamine iron qseC sepsis |
| url | https://journals.asm.org/doi/10.1128/mBio.02624-18 |
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