The Genome Sequence of Brucella abortus Vaccine Strain A19 Provides Insights on its Virulence Attenuation Compared to Brucella Abortus Strain 9-941

Background: Brucellosis is a widespread disease that affects animals and humans. The live attenuated Brucella abortus A19 strain is used for vaccination against brucellosis in China. In addition, the main mechanisms supporting the residual toxicity of A19 have not been elucidated. Here, we performed a comprehensive comparative analysis of the genome-wide sequence of A19 against the whole genome sequences of the published virulent reference strain 9-941. The primary objective of this study was to identify candidate virulence genes by systematically comparing the genomic sequences between the two genomes. Results: This analysis revealed two deletion regions in the A19 genome, in which all included large fragments of 63 bp, and one of their gene function is related to ABC transporter permease protein. In addition, we have identified minor mutations in important virulence-related genes that can be used to determine the underlying mechanisms of virulence attenuation. The function of its virulence gene covers LysR family transcriptional regulator, outer membrane, MFS transporter and oxidoreductase etc. At the same time, a PCR differential diagnosis method was constructed, which can distinguish A19, S19 and most other commonly used Brucella viruent strains and vaccine strains. Conclusion: The data may help to provide resources for further detailed analysis of mechanisms for other Brucella vaccines. It laid the foundation for further distinguishing between vaccine immunity and virulent strains infection.