title: Hfq, a novel pleiotropic regulator of virulence-associated genes in Francisella tularensis.
abstract: Francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. The ability to replicate within macrophages is central for virulence and relies on expression of genes located in the Francisella pathogenicity island (FPI), as well as expression of other genes. Regulation of FPI-encoded virulence gene expression in F. tularensis involves at least four regulatory proteins and is not fully understood. Here we studied the RNA-binding protein Hfq in F. tularensis and particularly the role that it plays as a global regulator of gene expression in stress tolerance and pathogenesis. We demonstrate that Hfq promotes resistance to several cellular stresses (including osmotic and membrane stresses). Furthermore, we show that Hfq is important for the ability of the F. tularensis vaccine strain LVS to induce disease and persist in organs of infected mice. We also demonstrate that Hfq is important for stress tolerance and full virulence in a virulent clinical isolate of F. tularensis, FSC200. Finally, microarray analyses revealed that Hfq regulates expression of numerous genes, including genes located in the FPI. Strikingly, Hfq negatively regulates only one of two divergently expressed putative operons in the FPI, in contrast to the other known regulators, which regulate the entire FPI. Hfq thus appears to be a new pleiotropic regulator of virulence in F. tularensis, acting mostly as a repressor, in contrast to the other regulators identified so far. Moreover, the results obtained suggest a novel regulatory mechanism for a subset of FPI genes.
authors.affiliation: Faculté de Médecine Necker, 156, rue de Vaugirard, 75730 Paris Cedex 15, France.
authors.forename: Karin L
authors.initials: KL
authors.lastname: Meibom
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Forslund
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kuoppa
authors.forename: Khaled
authors.initials: K
authors.lastname: Alkhuder
authors.forename: Iharilalao
authors.initials: I
authors.lastname: Dubail
authors.forename: Marion
authors.initials: M
authors.lastname: Dupuis
authors.forename: Ake
authors.initials: A
authors.lastname: Forsberg
authors.forename: Alain
authors.initials: A
authors.lastname: Charbit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D005604:Francisella tularensis / Q000502:physiology*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D044404:Genomic Islands; D035001:Host Factor 1 Protein / Q000502:physiology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016415:Sequence Alignment; D013312:Stress, Physiological; D016019:Survival Analysis; D014406:Tularemia / Q000382:microbiology / Q000473:pathology; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D035001:Host Factor 1 Protein; D037521:Virulence Factors