Virulence of MDR-TB strains

描述(申请人提供)：这项提案涉及当前结核病全球流行的一个重要因素，即NIAID最近发布的一份文件中指出的事实，即我们对新出现的结核分枝杆菌临床分离株几乎一无所知，其中许多是W-Beijing菌株。我们将在这里测试一个简单的假设，即与高传播率相关的这些菌株只是比低传播率的菌株毒力更强，第二个假设是，更强的毒力菌株通过产生调节性T细胞来逃避获得性免疫。这些简单的研究将提供关于传播性和毒力之间关系的重要基本信息，并且在R21应用的背景下是可行的。 公共卫生相关性：正如NIAID最近指出的一份重要文件所述，我们对新出现的临床结核病株几乎一无所知，其中许多属于W-Beijing家族。在这项拟议的研究中，我们将测量一组与旧金山地区一系列疫情有关的北京分离株的毒力。我们将在相关的豚鼠模型中检验一个简单的假设，即与高“传播率”相关的菌株比其他不易传播的菌株具有更高的毒力。

DESCRIPTION (provided by applicant): This proposal addresses an important element of the current tuberculosis global epidemic, namely the fact, recently stated in a document released by the NIAID, that we know next to nothing about the newly emerging clinical isolates of M. tuberculosis, many of which are W-Beijing strains. We will test the simple hypothesis here that such strains associated with high rates of transmission are simply more virulent than low transmission strains, with a secondary hypothesis being that the more virulent strains escape acquired immunity by generating regulatory T cells. These simple studies will provide important basic information about the relationship between transmissibility and virulence, and are doable within the context of an R21 application. PUBLIC HEALTH RELEVANCE: As an important NIAID document recently noted, we know almost nothing about the newly emerging clinical strains of tuberculosis, many of which are fall under the W-Beijing family. In this proposed study we will measure the virulence of a panel of Beijing isolates associated with a series of outbreaks in the San Francisco area. We will test the simple hypothesis that strains associated with high "transmissibility" are of higher virulence in the relevant guinea pig model compared to others that are not readily transmitted.