State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Beijing, China.
PLoS One. 2013 Aug 14;8(8):e70852. doi: 10.1371/journal.pone.0070852. eCollection 2013.
The Brucella melitensis vaccine strain M5 is widely used to prevent and control brucellosis in animals. In this study, we determined the whole-genome sequence of M5, and conducted a comprehensive comparative analysis against the whole-genome sequence of the virulent strain 16 M and other reference strains. This analysis revealed 11 regions of deletion (RDs) and 2 regions of insertion (RIs) within the M5 genome. Among these regions, the sequences encompassed in 5 RDs and 1 RI showed consistent variation, with a large deletion between the M5 and the 16 M genomes. RD4 and RD5 showed the large diversity among all Brucella genomes, both in RD length and RD copy number. Thus, RD4 and RD5 are potential sites for typing different Brucella strains. Other RD and RI regions exhibited multiple single nucleotide polymorphisms (SNPs). In addition, a genome fragment with a 56 kb rearrangement was determined to be consistent with previous studies. Comparative genomic analysis indicated that genomic island inversion in Brucella was widely present. With the genetic pattern common among all strains analyzed, these 2 RDs, 1 RI, and one inversion region are potential sites for detection of genomic differences. Several SNPs of important virulence-related genes (motB, dhbC, sfuB, dsbAB, aidA, aroC, and lysR) were also detected, and may be used to determine the mechanism of virulence attenuation. Collectively, this study reveals that comparative analysis between wild-type and vaccine strains can provide resources for the study of virulence and microevolution of Brucella.
布氏杆菌 M5 疫苗株被广泛用于预防和控制动物布鲁氏菌病。在本研究中，我们测定了 M5 的全基因组序列，并与强毒株 16M 和其他参考株的全基因组序列进行了全面比较分析。该分析揭示了 M5 基因组中存在 11 个缺失区（RDs）和 2 个插入区（RIs）。在这些区域中，包含在 5 个 RD 和 1 个 RI 中的序列表现出一致的变化，M5 和 16M 基因组之间存在较大的缺失。RD4 和 RD5 在所有布鲁氏菌基因组中表现出较大的多样性，无论是 RD 长度还是 RD 拷贝数。因此，RD4 和 RD5 是用于区分不同布鲁氏菌株的潜在位点。其他 RD 和 RI 区域表现出多个单核苷酸多态性（SNPs）。此外，确定一个包含 56kb 重排的基因组片段与之前的研究一致。比较基因组分析表明，布鲁氏菌中的基因组岛倒位广泛存在。根据所有分析菌株共有的遗传模式，这 2 个 RD、1 个 RI 和 1 个倒位区是检测基因组差异的潜在位点。还检测到了几个重要毒力相关基因（motB、dhbC、sfuB、dsbAB、aidA、aroC 和 lysR）的 SNP，这些 SNP 可能用于确定毒力衰减的机制。总之，本研究表明，野生型和疫苗株之间的比较分析可为布鲁氏菌的毒力和微观进化研究提供资源。
