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 |
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| Authors: | Fangkun Wang Zujian Qiao Sen Hu Wenxing Liu Huajun Zheng Sidang Liu Xiaomin Zhao Zhigao Bu |
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| 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, Chinaa;Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Taian, Shandong, Chinab;Shanghai-Ministry Key Laboratory of Disease and Health Genomics, Chinese National Human Genome Center, Shanghai, Chinac |
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| 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. |
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