Abstract
Francisella tularensis is a Gram-negative bacterium that causes a fatal human disease known as tularemia. The Centers for Disease Control and Prevention have classified F. tularensis as a category A tier 1 select agent. The virulence mechanisms of
are not entirely understood.
possesses very few transcription regulators, and most of these regulate the expression of genes involved in intracellular survival and virulence. The F. tularensis genome sequence analysis reveals an AraC (FTL_0689) transcriptional regulator homologous to the AraC/XylS family of transcriptional regulators. In Gram-negative bacteria, AraC activates genes required for l-arabinose utilization and catabolism. The role of the FTL_0689 regulator in F. tularensis is not known. In this study, we characterized the role of FTL_0689 in the gene regulation of F. tularensis and investigated its contribution to intracellular survival and virulence. The results demonstrate that FTL_0689 in
is not required for l-arabinose utilization. Instead, FTL_0689 specifically regulates the expression of the oxidative and global stress response, virulence, metabolism, and other key pathways genes required by
when exposed to oxidative stress. The
mutant is attenuated for intramacrophage growth and virulence in mice. Based on the deletion mutant phenotype,
was termed
(
xidative
tress
esponse
egulator). Altogether, this study elucidates the role of the
transcriptional regulator in tularemia pathogenesis.
The virulence mechanisms of category A select agent Francisella tularensis, the causative agent of a fatal human disease known as tularemia, remain largely undefined. The present study investigated the role of a transcriptional regulator and its overall contribution to the oxidative stress resistance of F. tularensis. The results provide an insight into a novel gene regulatory mechanism, especially when
is exposed to oxidative stress conditions. Understanding such
- specific regulatory mechanisms will help identify potential targets for developing effective therapies and vaccines to prevent tularemia.