M. bovis as a potentially more virulent MDR pathogen

描述（由申请人提供）：毒力可以定义为微生物在宿主防御中存活并引起疾病的能力。没有理由相信结核分枝杆菌的多药耐药（MDR）菌株比药物敏感（DS）菌株更毒力。bovis比M.结核病作为一种因此，如果M.牛被设计为MDR，它可能对公共卫生构成比MDRM更严重的威胁。结核拟议的研究将利用M. Ravenel菌株对小鼠的上级毒力。以确定上级毒力是否与肺中诱导更高水平的Th 1免疫表达的能力相关，所述毒力表现为诱导肺病理学更快发展和导致更早死亡的能力。这将通过测量肺中Th 1细胞因子、促炎细胞因子和趋化因子的基因表达水平来研究。Elispot和流式细胞术将用于计数IFN-？的总数，在肺中产生病原体特异性的CD 4和CD 8 T细胞。M.牛支原体也与较高水平的细菌基因表达相关，记住M. bovis Ravenel和M.肺结核引起相同程度的静止性肺部感染。将使用实时RT-PCR测量病原体基因表达水平，以每个肺和每个CFU的mRNA拷贝数表示。M.结核和M.牛染色体，包括esat 6和cfp-10，将受到关注。结果表明，该菌的毒力较强。bovis和M.将比较结核菌株。

DESCRIPTION (PROVIDED BY APPLICANT): Virulence may be defined as the ability of a microorganism to survive host defenses and cause disease. There is no reason to believe that multi-drug resistant (MDR) strains of Mycobacterium tuberculosis are more virulent than drug sensitive (DS) strains There is evidence, on the other hand, that M. bovis is much more virulent than M. tuberculosis as a species. Therefore, if M. bovis were engineered to be MDR, it could pose a more serious threat to public health than MDRM. tuberculosis. The proposed research will use the superior virulence for mice of the Ravenel strain of M. bovis over M tuberculosis H37Rv to determine whether superior virulence, as manifest by ability to induce faster development of lung pathology and cause earlier death, is associated with the ability to induce a higher level of expression of Th1 immunity in the lung. This will be investigated by measuring levels of expression of genes for Th1 cytokines, proinflammatory cytokines and chemokines in the lungs. Elispot and flow cytometry will be used to enumerate total numbers of IFN-?, producing, pathogen-specific CD4 and CD8 T cells in the lungs. The possibility that superior virulence of M. bovis is also associated with higher levels of bacterial gene expression will be investigated, keeping in mind that M. bovis Ravenel and M. tuberculosis cause the same level of stationary lung infection. Real-time RT-PCR will be used to measure levels of pathogen gene expression in terms of mRNA copy number per lung and per CFU. Genes within the RD1 region of the M. tuberculosis and M. bovis chromosome, including esat6 and cfp-10, will receive attention. The virulence of a number of M. bovis and M. tuberculosis strains will be compared.