Inactivation of formyltransferase (wbkC) gene generates a Brucella abortus rough strain that is attenuated in macrophages and in mice

Vaccine. 2010 Aug 2;28(34):5627-34. doi: 10.1016/j.vaccine.2010.06.023. Epub 2010 Jun 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / immunology
  • Brucella Vaccine / immunology*
  • Brucella abortus / enzymology*
  • Brucella abortus / genetics
  • Brucella abortus / immunology
  • Brucella abortus / pathogenicity
  • Brucellosis / immunology*
  • Brucellosis / microbiology
  • Hydroxymethyl and Formyl Transferases / genetics
  • Hydroxymethyl and Formyl Transferases / metabolism*
  • Interleukin-12 / immunology
  • Macrophages / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation
  • Tumor Necrosis Factor-alpha / immunology
  • Vaccines, Attenuated / immunology
  • Virulence

Substances

  • Brucella Vaccine
  • Tumor Necrosis Factor-alpha
  • Vaccines, Attenuated
  • Interleukin-12
  • Hydroxymethyl and Formyl Transferases