title: Deletion of IglH in virulent Francisella tularensis subsp. holarctica FSC200 strain results in attenuation and provides protection against the challenge with the parental strain.
abstract: Francisella tularensis, the causative agent of tularemia, is a highly infectious intracellular pathogen with no licensed vaccine available today. The recent search for genome sequences involved in F. tularensis virulence mechanisms led to the identification of the 30-kb region defined as a Francisella pathogenicity island (FPI). In our previous iTRAQ study we described the concerted upregulation of some FPI proteins in different F. tularensis strains cultivated under stress conditions. Among them we identified the IglH protein whose role in Francisella virulence has not been characterized yet. In this work we deleted the iglH gene in a European clinical isolate of F. tularensis subsp. holarctica FSC200. We showed that the iglH gene is necessary for intracellular growth and escape of F. tularensis from phagosomes. We also showed that the iglH mutant is avirulent in a mouse model of infection and persists in the organs for about three weeks after infection. Importantly, mice vaccinated by infection with the iglH mutant were protected against subcutaneous challenge with the fully virulent parental FSC200 strain. This is the first report of a defined subsp. holarctica FPI deletion strain that provides protective immunity against subsequent subcutaneous challenge with a virulent isolate of F. tularensis subsp. holarctica.
authors.affiliation: Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 50001 Hradec Kralove, Czech Republic. straskova@pmfhk.cz
authors.forename: Adela
authors.initials: A
authors.lastname: Straskova
authors.forename: Lukas
authors.initials: L
authors.lastname: Cerveny
authors.forename: Petra
authors.initials: P
authors.lastname: Spidlova
authors.forename: Vera
authors.initials: V
authors.lastname: Dankova
authors.forename: Davor
authors.initials: D
authors.lastname: Belcic
authors.forename: Marina
authors.initials: M
authors.lastname: Santic
authors.forename: Jiri
authors.initials: J
authors.lastname: Stulik
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005604:Francisella tularensis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D005816:Genetic Complementation Test; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010588:Phagosomes / Q000382:microbiology; D017384:Sequence Deletion; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated