Limited role for iron regulation in Coxiella burnetii Pathogenesis

Heather L. Briggs, Nicolein Pul, Rekha Seshadri, Mary J. Wilson, Claudia Tersteeg, Kasi E. Russell-Lodrigue, Masako Andoh, Andreas J. Bäumler, James E. Samuel

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

In gram-negative bacteria, iron acquisition proteins are commonly regulated by Fur (ferric uptake regulator), which binds iron-regulated promoters (the 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 Escherichia coli fur deletion mutant. A ferrous iron transporter gene (CBU1766), a putative iron binding protein-encoding gene (CBU0970), and a cation efflux pump gene (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 twofold 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 in comparison to growth under iron-replete conditions. In an iron-overloaded animal model in vivo, the level of bacterial growth detected in the iron-injected animals was significantly decreased in comparison to growth in control animals. 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 requirement of a low level of iron for survival, perhaps to avoid creation of additional reactive oxygen radicals.

Original languageEnglish (US)
Pages (from-to)2189-2201
Number of pages13
JournalInfection and immunity
Volume76
Issue number5
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Briggs, H. L., Pul, N., Seshadri, R., Wilson, M. J., Tersteeg, C., Russell-Lodrigue, K. E., Andoh, M., Bäumler, A. J., & Samuel, J. E. (2008). Limited role for iron regulation in Coxiella burnetii Pathogenesis. Infection and immunity, 76(5), 2189-2201. https://doi.org/10.1128/IAI.01609-07