Hewinson R Glyn, Vordermeier H Martin, Smith Noel H, Gordon Stephen V
TB Research Group, Veterinary Laboratories Agency, Weybridge, Addlestone, Surrey KT15 3NB, UK.
Vet Microbiol. 2006 Feb 25;112(2-4):127-39. doi: 10.1016/j.vetmic.2005.11.050. Epub 2005 Dec 27.
Significant and rapid progress has been made in our knowledge and understanding of Mycobacterium bovis since the last international M. bovis conference 5 years ago. Much of this progress has been underpinned by the completion of the genome sequence. This important milestone has catalysed research into the development of a number of improved tools with which to combat bovine tuberculosis. In this article we will review recent progress made in the development of these tools and in our understanding of the organism, its evolution and spread. Comparison of the genome sequence with those of other members of the Mycobacterium tuberculosis complex has enabled insights into the evolution of M. bovis. This analysis also indicates that the M. tuberculosis complex have the propensity to adapt to new host species. The use of high throughput molecular typing methods has revealed that the recent bovine tuberculosis epidemic in Great Britain is being driven by a number of clonal expansions, which cannot be explained by random mutation and drift alone. Completion of a number of mycobacterial genome sequences has allowed the development of antigen mining techniques that rapidly identify M. bovis-specific genes. These can then be used as reagents in the gamma interferon assay to increase the specificity of the assay and also to discriminate between Bacillus of Calmette and Guérin (BCG) vaccinated animals and those infected with M. bovis. In the longer term, comparisons between the genomes of M. bovis and BCG will allow insight into how BCG became attenuated following serial passage on artificial growth media and reveal clues into how to improve the vaccine efficacy of BCG.
自5年前召开上一届国际牛分枝杆菌会议以来,我们在牛分枝杆菌的知识和理解方面取得了重大且迅速的进展。这一进展很大程度上得益于基因组序列的完成。这一重要里程碑推动了对多种改进工具的开发研究,以对抗牛结核病。在本文中,我们将回顾这些工具开发方面以及我们对该生物体、其进化和传播的理解方面取得的最新进展。将牛分枝杆菌的基因组序列与结核分枝杆菌复合群其他成员的序列进行比较,有助于深入了解牛分枝杆菌的进化。该分析还表明,结核分枝杆菌复合群有适应新宿主物种的倾向。高通量分子分型方法的应用表明,英国近期的牛结核病疫情是由一些克隆扩增驱动的,这不能仅用随机突变和漂变来解释。多个分枝杆菌基因组序列的完成使得抗原挖掘技术得以发展,这些技术能够快速识别牛分枝杆菌特异性基因。然后这些基因可作为γ干扰素检测中的试剂,以提高检测的特异性,并区分接种卡介苗的动物和感染牛分枝杆菌的动物。从长远来看,比较牛分枝杆菌和卡介苗的基因组将有助于深入了解卡介苗在人工生长培养基上连续传代后如何减毒,并揭示提高卡介苗疫苗效力的线索。