The iron response regulator Irr controls iron homoeostasis in Brucella

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

David A. Martinson (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Members of the genus Brucella are small, Gram-negative intracellular bacterial pathogens that are capable of infecting a wide range of mammalian hosts including humans. Brucella primarily reside inside of host macrophages. As an intracellular pathogen, Brucella must overcome iron sequestration in the host cell by utilizing highly efficient iron transport systems. These systems must be tightly regulated, however, as excess intracellular iron is toxic to the bacterial cells. Most of the alpha-proteobacteria rely on a transcriptional regulator called the iron response regulator (Irr) to control the expression of their iron metabolism genes. The work presented in this dissertation provides evidence to support the proposition that the Irr protein is the main iron-responsive transcriptional regulator in Brucella. Irr serves as an activator of genes coding for products that are involved in iron acquisition and a repressor of genes for products that require high levels of iron for their function, or serve as iron export and storage proteins when cellular iron levels are low. Irr is a conditionally stable protein that is present when cellular iron levels are low, and is degraded when cellular iron levels are high. Irr activity is controlled by inactivation and degradation through its interaction with heme, which is synthesized when cellular iron levels rise. Brucella has another iron-responsive regulator that is also found in some members of the alpha-proteobacteria called the rhizobial iron regulator (RirA). RirA is active when cellular iron levels are high, and its regulon partially overlaps with that of Irr in Brucella. The activity of Irr when cellular iron levels are low, and the activity of RirA when cellular iron levels are high, ensures that cellular iron levels are maintained at physiological levels, protecting against iron starvation, and against iron related toxicity in Brucella.

Additional Information

Publication

Dissertation

Language: English

Date: 2023

Subjects

Microbiology;Brucella;Fur;Iron;Irr;RirA

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