title: Comparison of genomes of Brucella melitensis M28 and the B. melitensis M5-90 derivative vaccine strain highlights the translation elongation factor Tu gene tuf2 as an attenuation-related gene.
abstract: Brucella melitensis causes brucellosis, a disease affecting sheep, cattle, and sometimes humans. Attenuated B. melitensis strain M5-90, derived from virulent strain M28, is widely used as a live vaccine in ruminants in China. Genetic differences between the strains may cast light on the mechanism of attenuation. We recently reported the complete genomic sequences of M28 and M5-90. Genome organization is highly conserved between these isolates, and also with virulent strains 16 M and ATCC 23457. Analysis revealed 23 open reading frames (ORFs) with consistent differences between M5-90 and the virulent strains. Notably, the tuf2 gene encoding translation elongation factor EF-Tu from M5-90 contained 50 single nucleotide polymorphisms (SNPs) and 9 gaps (indels) compared to tuf2 of M28 or of the other virulent strains. There were no changes in tuf1. To evaluate the potential role of EF-Tu in pathogenesis, tuf1 and tuf2 mutants of M28 and an M5-90 strain harboring wild-type tuf2 were constructed, and their virulence/attenuation was evaluated in vivo. We report that the tuf2 gene plays an important role in the attenuation of M5-90 virulence.
authors.affiliation: State Key Laboratory of Veterinary Biotechnology and Zoonosis Laboratory of the Ministry of Agriculture, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China.
authors.forename: Fangkun
authors.initials: F
authors.lastname: Wang
authors.forename: Zujian
authors.initials: Z
authors.lastname: Qiao
authors.forename: Sen
authors.initials: S
authors.lastname: Hu
authors.forename: Wenxing
authors.initials: W
authors.lastname: Liu
authors.forename: Huajun
authors.initials: H
authors.lastname: Zheng
authors.forename: Sidang
authors.initials: S
authors.lastname: Liu
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhao
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Bu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002004:Brucella Vaccine / Q000235:genetics* / Q000276:immunology; D017347:Brucella melitensis / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D002006:Brucellosis / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D005260:Female; D016680:Genome, Bacterial; D051379:Mice; D008969:Molecular Sequence Data; D010444:Peptide Elongation Factor Tu / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D002004:Brucella Vaccine; D014613:Vaccines, Attenuated; D010444:Peptide Elongation Factor Tu