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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Salmonella Typhimurium catecholamine dopamine iron qseC sepsis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/57f584f7f41d47c996f27ad5c95554b5
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spelling	oai:doaj.org-article:57f584f7f41d47c996f27ad5c95554b52021-11-15T15:55:13ZDopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice10.1128/mBio.02624-182150-7511https://doaj.org/article/57f584f7f41d47c996f27ad5c95554b52019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02624-18https://doaj.org/toc/2150-7511ABSTRACT 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.Stefanie DichtlEgon DemetzDavid HaschkaPiotr TymoszukVerena PetzerManfred NairzMarkus SeifertAlexander HoffmannNatascha BrigoReinhard WürznerIgor TheurlJoyce E. KarlinseyFerric C. FangGünter WeissAmerican Society for MicrobiologyarticleSalmonella TyphimuriumcatecholaminedopamineironqseCsepsisMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Salmonella Typhimurium catecholamine dopamine iron qseC sepsis Microbiology QR1-502
spellingShingle	Salmonella Typhimurium catecholamine dopamine iron qseC sepsis Microbiology QR1-502 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
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.
format	article
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
title	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_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_sort	dopamine is a siderophore-like iron chelator that promotes <italic toggle="yes">salmonella enterica</italic> serovar typhimurium virulence in mice
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/57f584f7f41d47c996f27ad5c95554b5
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Dopamine Is a Siderophore-Like Iron Chelator That Promotes <italic toggle="yes">Salmonella enterica</italic> Serovar Typhimurium Virulence in Mice

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