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Pivotal role of the Francisella tularensis heat-shock sigma factor RpoH

¹ Université Paris Descartes, Faculté de Médecine Necker-Enfants Malades, F-75015 Paris, France
² INSERM, U570, Unit of Pathogenesis of Systemic Infections, F-75015 Paris, France
³ Channing Laboratories, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
⁴ Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, MD 20815-6789, USA

Francisella tularensis is a highly infectious pathogen that infects animals and humans to cause the disease tularemia. The primary targets of this bacterium are macrophages, in which it replicates in the cytoplasm after escaping the initial phagosomal compartment. The ability to replicate within macrophages relies on the tightly regulated expression of a series of genes. One of the most commonly used means of coordinating the regulation of multiple genes in bacteria consists of the association of dedicated alternative sigma factors with the core of the RNA polymerase (RNAP). In silico analysis of the F. tularensis LVS genome led us to identify, in addition to the genes encoding the RNAP core (comprising the 1, 2, β, β' and subunits), one gene (designated rpoD) encoding the major sigma factor ⁷⁰, and a unique gene (FTL_0851) encoding a putative alternative sigma factor homologue of the ³² heat-shock family (designated rpoH). Hence, F. tularensis represents one of the minority of bacterial species that possess only one or no alternative sigma factor in addition to the main factor ⁷⁰. In the present work, we show that FTL_0851 encodes a genuine ³² factor. Transcriptomic analyses of the F. tularensis LVS heat-stress response allowed the identification of a series of orthologues of known heat-shock genes (including those for Hsp40, GroEL, GroES, DnaK, DnaJ, GrpE, ClpB and ClpP) and a number of genes implicated in Francisella virulence. A bioinformatic analysis was used to identify genes preceded by a putative ³²-binding site, revealing both similarities to and differences from RpoH-mediated gene expression in Escherichia coli. Our results suggest that RpoH is an essential protein of F. tularensis, and positively regulates a subset of genes involved in the heat-shock response.

Correspondence
Karin L. Meibom
karin.meibom{at}inserm.fr

The microarray data discussed in this paper have been deposited in ArrayExpress under the accession numbers E-MEXP-2048 and E-MEXP-2037.

Five supplementary tables, listing primers used in this study, genes significantly decreased in expression after temperature upshift, genes that were used in BioProspector analysis, putative binding sites found by BioProspector and used for building of matrices, and genes with a potential ³²-binding sequence in their promoter region, are available with the online version of this paper.