title: Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice.
abstract: Rough mutants of Brucella abortus were generated by disruption of wbkC gene which encodes the formyltransferase enzyme involved in LPS biosynthesis. In bone marrow-derived macrophages the B. abortusDeltawbkC mutants were attenuated, could not reach a replicative niche and induced higher levels of IL-12 and TNF-alpha when compared to parental smooth strains. Additionally, mutants exhibited attenuation in vivo in C57BL/6 and interferon regulatory factor-1 knockout mice. DeltawbkC mutant strains induced lower protective immunity in C56BL/6 than smooth vaccine S19 but similar to rough vaccine RB51. Finally, we demonstrated that Brucella wbkC is critical for LPS biosynthesis and full bacterial virulence.
authors.affiliation: Department of Biochemistry and Immunology, Federal University of Minas Gerais, Pampulha, Belo Horizonte, MG, Brazil.
authors.forename: Thaís Lourdes Santos
authors.initials: TL
authors.lastname: Lacerda
authors.forename: Patrícia Gomes
authors.initials: PG
authors.lastname: Cardoso
authors.forename: Leonardo
authors.initials: L
authors.lastname: Augusto de Almeida
authors.forename: Ilana Lopes Baratella da Cunha
authors.initials: IL
authors.lastname: Camargo
authors.forename: Daniela Almeida Freitas
authors.initials: DA
authors.lastname: Afonso
authors.forename: Cyntia Cardoso
authors.initials: CC
authors.lastname: Trant
authors.forename: Gilson Costa
authors.initials: GC
authors.lastname: Macedo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Campos
authors.forename: Silvio L
authors.initials: SL
authors.lastname: Cravero
authors.forename: Suzana P
authors.initials: SP
authors.lastname: Salcedo
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gorvel
authors.forename: Sérgio Costa
authors.initials: SC
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D002004:Brucella Vaccine / Q000276:immunology*; D002003:Brucella abortus / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D002006:Brucellosis / Q000276:immunology* / Q000382:microbiology; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics / Q000378:metabolism*; D018664:Interleukin-12 / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014774:Virulence
chemical_list: D002004:Brucella Vaccine; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D018664:Interleukin-12; D019877:Hydroxymethyl and Formyl Transferases