Key Laboratory of Clinical Diagnosis and Treatment Technology in Animal Disease, Ministry of Agriculture/College of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia 010018, China; Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention, Hohhot, Inner Mongolia 010031, China.
College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
Gene. 2022 Jul 1;830:146521. doi: 10.1016/j.gene.2022.146521. Epub 2022 Apr 18.
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.
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.
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.
布氏杆菌病是一种广泛存在于动物和人类中的疾病。在中国,活疫苗减毒布鲁氏菌 abortus A19 株被用于预防布氏杆菌病。此外,支持 A19 残余毒性的主要机制尚未阐明。在这里,我们对 A19 与已发表的毒力参考菌株 9-941 的全基因组序列进行了全面的比较分析。本研究的主要目的是通过系统比较两个基因组的基因组序列来鉴定候选毒力基因。
该分析揭示了 A19 基因组中的两个缺失区域,其中都包含 63bp 的大片段,它们的一个基因功能与 ABC 转运体透性蛋白有关。此外,我们还鉴定了重要毒力相关基因中的微小突变,可用于确定毒力衰减的潜在机制。其毒力基因的功能涵盖了 LysR 家族转录调节因子、外膜、MFS 转运蛋白和氧化还原酶等。同时,构建了一种 PCR 差异诊断方法,可区分 A19、S19 和大多数其他常用的布氏杆菌毒力菌株和疫苗菌株。
这些数据可能有助于为进一步分析其他布鲁氏菌疫苗的机制提供资源。它为进一步区分疫苗免疫和毒力株感染奠定了基础。