title: Characterization of tetratricopeptide repeat-like proteins in Francisella tularensis and identification of a novel locus required for virulence.
abstract: Francisella tularensis is a highly infectious bacterium that causes the potentially lethal disease tularemia. This extremely virulent bacterium is able to replicate in the cytosolic compartments of infected macrophages. To invade macrophages and to cope with their intracellular environment, Francisella requires multiple virulence factors, which are still being identified. Proteins containing tetratricopeptide repeat (TPR)-like domains seem to be promising targets to investigate, since these proteins have been reported to be directly involved in virulence-associated functions of bacterial pathogens. Here, we studied the role of the FTS_0201, FTS_0778, and FTS_1680 genes, which encode putative TPR-like proteins in Francisella tularensis subsp. holarctica FSC200. Mutants defective in protein expression were prepared by TargeTron insertion mutagenesis. We found that the locus FTS_1680 and its ortholog FTT_0166c in the highly virulent Francisella tularensis type A strain SchuS4 are required for proper intracellular replication, full virulence in mice, and heat stress tolerance. Additionally, the FTS_1680-encoded protein was identified as a membrane-associated protein required for full cytopathogenicity in macrophages. Our study thus identifies FTS_1680/FTT_0166c as a new virulence factor in Francisella tularensis.
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic Institute of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Vera
authors.initials: V
authors.lastname: Dankova
authors.affiliation: Institute of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Balonova
authors.affiliation: Institute of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Adela
authors.initials: A
authors.lastname: Straskova
authors.affiliation: Institute of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Spidlova
authors.affiliation: Institute of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Daniela
authors.initials: D
authors.lastname: Putzova
authors.affiliation: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Kijek
authors.affiliation: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Bozue
authors.affiliation: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Cote
authors.affiliation: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Mou
authors.affiliation: Bacteriology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Worsham
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Szotakova
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University in Prague, Hradec Kralove, Czech Republic cervenyl@faf.cuni.cz.
authors.forename: Lukas
authors.initials: L
authors.lastname: Cerveny
authors.affiliation: Institute of Molecular Pathology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Stulik
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D005604:Francisella tularensis / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D055786:Gene Knockout Techniques; D056426:Genetic Loci; D008264:Macrophages / Q000382:microbiology; D008807:Mice, Inbred BALB C; D016254:Mutagenesis, Insertional; D014406:Tularemia / Q000382:microbiology / Q000473:pathology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors