title: A Francisella tularensis SCHU S4 mutant deficient in γ-glutamyltransferase activity induces protective immunity: characterization of an attenuated vaccine candidate.
abstract: Francisella tularensis is an intracellular pathogen which causes tularaemia. There is no licensed vaccine currently available for prophylaxis. The γ-glutamyl transpeptidase (GGT) encoded by the ggt gene has been shown to be important for the intracellular survival of F. tularensis. In this study we have constructed a ggt deletion mutant in the highly virulent F. tularensis strain SCHU S4. Characterization of the mutant strain confirmed the function of ggt, and confirmed the role of GGT in cysteine acquisition. The mutant strain was highly attenuated both in vitro and in vivo using murine models of infection. Moreover, we have demonstrated that the attenuated mutant is able to induce protective immunity against an F. tularensis SCHU S4 challenge, and thus may be a candidate for the development of an attenuated vaccine.
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Ireland
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Helen
authors.initials: H
authors.lastname: LeButt
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Thomas
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
authors.forename: Petra C F
authors.initials: PCF
authors.lastname: Oyston
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D005260:Female; D005604:Francisella tularensis / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D005816:Genetic Complementation Test; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D017384:Sequence Deletion; D014406:Tularemia / Q000276:immunology* / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence; D005723:gamma-Glutamyltransferase / Q000235:genetics*
chemical_list: D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D005723:gamma-Glutamyltransferase