Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability

ABSTRACT Coxiella burnetii, the causative agent of Query (Q) fever in humans, is a highly infectious obligate intracellular bacterium. Following uptake into a host cell, C. burnetii replicates within a phagolysosome-derived compartment referred to as the Coxiella-containing vacuole (CCV). During inf...

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Autores principales:	Savannah E. Sanchez, Anders Omsland
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Coxiella burnetii axenic virulence iron bacteriology physiology Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2e047ab9c23049f8bd825495d58259c0
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spelling	oai:doaj.org-article:2e047ab9c23049f8bd825495d58259c02021-11-15T15:30:51ZCritical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability10.1128/mSphere.00458-202379-5042https://doaj.org/article/2e047ab9c23049f8bd825495d58259c02020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00458-20https://doaj.org/toc/2379-5042ABSTRACT Coxiella burnetii, the causative agent of Query (Q) fever in humans, is a highly infectious obligate intracellular bacterium. Following uptake into a host cell, C. burnetii replicates within a phagolysosome-derived compartment referred to as the Coxiella-containing vacuole (CCV). During infection, C. burnetii exhibits tropism for tissues related to iron storage and recycling (e.g., the liver and splenic red pulp), suggesting that pathogen physiology is linked to host iron metabolism. Iron has been described to have a limited role in C. burnetii virulence regulation, despite evidence that C. burnetii-infected host cells increase expression of transferrin receptors, thereby suggesting that active iron acquisition by the bacterium occurs upon infection. Through the use of host cell-free culture, C. burnetii was separated from the host cell in order to directly assess the role of different forms of iron in C. burnetii replication and viability, and therefore virulence. Results indicate that C. burnetii tolerates molecular iron over a broad concentration range (i.e., ∼0.001 to 1 mM) and undergoes gross loss of viability upon iron starvation. C. burnetii protein synthesis and energy metabolism, however, occur nearly uninhibited under iron concentrations not permissive to replication. Despite the apparent absence of genes related to acquisition of host-associated iron-containing proteins, C. burnetii replication is supported by hemoglobin, transferrin, and ferritin, likely due to release of iron from such proteins under acidic conditions. Moreover, chelation of host iron pools inhibited pathogen replication during infection of cultured cells. IMPORTANCE Host organisms restrict the availability of iron to invading pathogens in order to reduce pathogen replication. To counteract the host’s response to infection, bacteria can rely on redundant mechanisms to obtain biologically diverse forms of iron during infection. C. burnetii appears specifically dependent on molecular iron for replication and viability and exhibits a response to iron akin to bacteria that colonize iron-rich environments. Physiological adaptation of C. burnetii to the unique acidic and degradative environment of the CCV is consistent with access of this pathogen to molecular iron.Savannah E. SanchezAnders OmslandAmerican Society for MicrobiologyarticleCoxiella burnetiiaxenicvirulenceironbacteriologyphysiologyMicrobiologyQR1-502ENmSphere, Vol 5, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Coxiella burnetii axenic virulence iron bacteriology physiology Microbiology QR1-502
spellingShingle	Coxiella burnetii axenic virulence iron bacteriology physiology Microbiology QR1-502 Savannah E. Sanchez Anders Omsland Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability
description	ABSTRACT Coxiella burnetii, the causative agent of Query (Q) fever in humans, is a highly infectious obligate intracellular bacterium. Following uptake into a host cell, C. burnetii replicates within a phagolysosome-derived compartment referred to as the Coxiella-containing vacuole (CCV). During infection, C. burnetii exhibits tropism for tissues related to iron storage and recycling (e.g., the liver and splenic red pulp), suggesting that pathogen physiology is linked to host iron metabolism. Iron has been described to have a limited role in C. burnetii virulence regulation, despite evidence that C. burnetii-infected host cells increase expression of transferrin receptors, thereby suggesting that active iron acquisition by the bacterium occurs upon infection. Through the use of host cell-free culture, C. burnetii was separated from the host cell in order to directly assess the role of different forms of iron in C. burnetii replication and viability, and therefore virulence. Results indicate that C. burnetii tolerates molecular iron over a broad concentration range (i.e., ∼0.001 to 1 mM) and undergoes gross loss of viability upon iron starvation. C. burnetii protein synthesis and energy metabolism, however, occur nearly uninhibited under iron concentrations not permissive to replication. Despite the apparent absence of genes related to acquisition of host-associated iron-containing proteins, C. burnetii replication is supported by hemoglobin, transferrin, and ferritin, likely due to release of iron from such proteins under acidic conditions. Moreover, chelation of host iron pools inhibited pathogen replication during infection of cultured cells. IMPORTANCE Host organisms restrict the availability of iron to invading pathogens in order to reduce pathogen replication. To counteract the host’s response to infection, bacteria can rely on redundant mechanisms to obtain biologically diverse forms of iron during infection. C. burnetii appears specifically dependent on molecular iron for replication and viability and exhibits a response to iron akin to bacteria that colonize iron-rich environments. Physiological adaptation of C. burnetii to the unique acidic and degradative environment of the CCV is consistent with access of this pathogen to molecular iron.
format	article
author	Savannah E. Sanchez Anders Omsland
author_facet	Savannah E. Sanchez Anders Omsland
author_sort	Savannah E. Sanchez
title	Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability
title_short	Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability
title_full	Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability
title_fullStr	Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability
title_full_unstemmed	Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability
title_sort	critical role for molecular iron in <named-content content-type="genus-species">coxiella burnetii</named-content> replication and viability
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/2e047ab9c23049f8bd825495d58259c0
work_keys_str_mv	AT savannahesanchez criticalroleformolecularironinnamedcontentcontenttypegenusspeciescoxiellaburnetiinamedcontentreplicationandviability AT andersomsland criticalroleformolecularironinnamedcontentcontenttypegenusspeciescoxiellaburnetiinamedcontentreplicationandviability
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Critical Role for Molecular Iron in <named-content content-type="genus-species">Coxiella burnetii</named-content> Replication and Viability

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