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Infect. Immun. doi:10.1128/IAI.01609-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A limited role for iron regulation in Coxiella burnetii pathogenesis

TAMUS Health Science Center, Department of Microbial and Molecular Pathogenesis, College Station, Texas; The Institute of Genomic Research, Rockville, Maryland; University of California, Department of Medical Microbiology and Immunology, Davis, California

^* To whom correspondence should be addressed. Email: jsamuel{at}tamhsc.edu.

	Abstract

In gram-negative bacteria, iron acquisition proteins are commonly regulated by Fur, ferric uptake regulator that binds iron-regulated promoters ("Fur Box"). We hypothesized that Coxiella burnetii requires iron and employs an iron regulatory system and used various approaches to define a Fur regulon. Cloned C. burnetii fur complemented an E. coli fur deletion mutant. A ferrous iron transporter (CBU1766), a putative iron binding protein (CBU0970) and a cation efflux pump (CBU1362) were identified by genome annotation and using a Fur titration assay. Bioinformatically predicted Fur box-containing promoters were tested for transcriptional control by iron. Five genes demonstrated at least a 2-fold induction with minimal iron. Putatively regulated genes were evaluated in a two-plasmid regulator/promoter heterologous expression system. These data suggested a very limited Fur regulated system in C. burnetii. In an in vitro tissue culture model, a significant increase in bacterial growth was observed with infected cells treated with deferoxamine compared to iron replete conditions. In an iron overload animal model in vivo, a significant decrease in bacterial growth was detected in the iron-injected animals compared to control. In a low iron diet animal model, a significant increase in splenomegaly was observed, but no significant change in bacterial growth was identified. The small number of predicted iron acquisition systems, few Fur-regulated genes, and enhanced replication under a decreased iron level predict a low requirement of iron for survival, perhaps to avoid creation of additional reactive oxygen radicals.