Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice.
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.
Lacerda
Thaís Lourdes Santos
TL
Department of Biochemistry and Immunology, Federal University of Minas Gerais, Pampulha, Belo Horizonte, MG, Brazil.
Cardoso
Patrícia Gomes
PG
Augusto de Almeida
Leonardo
L
Camargo
Ilana Lopes Baratella da Cunha
IL
Afonso
Daniela Almeida Freitas
DA
Trant
Cyntia Cardoso
CC
Macedo
Gilson Costa
GC
Campos
Eleonora
E
Cravero
Silvio L
SL
Salcedo
Suzana P
SP
Gorvel
Jean-Pierre
JP
Oliveira
Sérgio Costa
SC
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
D002004:Brucella Vaccine; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D018664:Interleukin-12; D019877:Hydroxymethyl and Formyl Transferases