Virulence of MDR-TB strains

耐多药结核菌株的毒力

基本信息

批准号：
8234900
负责人：
IAN M ORME
金额：
$ 18.54万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-15 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8234900
关键词：
Address Aerosols Animal Model Area Bacillus (bacterium)Biological Biology California Cavia Cells Clinical Communities Data Disease Outbreaks Disease Progression Dose Elements Epidemic Epidemiologic Studies Exhibits Family Genomics Gold Histopathology Human Immune Immune response Infection Laboratories Letters Lung Measures Modeling Monitor Multiple drug resistant Mycobacteria Tuberculosis Mycobacterium tuberculosis National Institute of Allergy and Infectious Disease Organism Pathogenesis Pathogenicity Pathology Protocols documentation Publishing Recommendation Regulatory T-Lymphocyte Research Research Priority San Francisco Series Source Testing Time Tuberculosis Tuberculosis Vaccines United States National Institutes of Health Universities Vaccination Virulence Virulent Work acquired immunity base falls mouse model protective effect research study transmission process vaccine candidate

项目摘要

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.

描述（由申请人提供）：该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-北京毒株。我们将在这里测试一个简单的假设，即与高传播率相关的菌株比低传播率菌株的毒性更强，第二个假设是毒性更强的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有关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 最近的一份重要文件指出的那样，我们对新出现的结核病临床菌株几乎一无所知，其中许多属于 W-Beijing 家族。在这项拟议的研究中，我们将测量与旧金山地区一系列疫情相关的一组北京分离株的毒力。我们将测试一个简单的假设，即与其他不易传播的菌株相比，与高“传染性”相关的菌株在相关豚鼠模型中具有更高的毒力。