Genomic and immunological comparisons of M africanum and M tuberculosis

非洲分枝杆菌和结核分枝杆菌的基因组和免疫学比较

• 批准号: 7341783
• 负责人: BOUKE C DE JONG
• 金额: $ 11.98万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-18 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7341783
• 关键词: 5-(6)-carboxyfluorescein diacetate succinimidyl ester; Abbreviations; Africa; Antibodies; Antigens; Attenuated; Award; Bacteria; Biological Assay; CD4 Lymphocyte Count; Cells; Colony-forming units; Communities; Complex; Data; Development; Diagnosis; Diagnostic tests; Disease; Esters; Excision; Flow Cytometry; Gambia; Gene Expression Profile; Genes; Genetic; Genetic Polymorphism; Genome; Genomics; Genotype; Guinea-Bissau; HIV; Household; Immune; Immune response; Immunization; Immunosuppressive Agents; Incidence; Infection; Intention; International; Lead; Measures; Modeling; Mycobacterium tuberculosis; Nomenclature; Numbers; Opportunistic Infections; Organism; Pathogenesis; Patients; Peripheral Blood Mononuclear Cell; Phenotype; Prevalence; Proteins; RNA; Rate; Relative (related person); Research; Reverse Transcription; Sampling; Sputum; Staining method; Stains; Surface; Testing; Time; Tissue-Specific Gene Expression; Tuberculosis; Vaccines; Work; cytokine; disorder control; enzyme linked immunospot assay; follow-up; genome sequencing; immunogenicity; insight; latent infection; member; mycobacterial; novel diagnostics; research and development; response; tool; transmission process; tuberculosis treatment

DESCRIPTION (provided by applicant): During the first International Research Development Award, Dr. de Jong moved to the Gambia in 2003. Her intention was to identify M. tuberculosis strains particularly well suited for transmission and cavitation; however a fortuitous split between M. africanum and M. tuberculosis allowed her to compare transmission, cavitation, and other phenotypes between two phylogenetically distinct members of the M. tuberculosis complex. This analysis showed that 1) both patients infected with and contacts of M. africanum have a blunted immune responses to Early Secretory Antigen 6 (ESAT-6),which has relevance to the development of diagnostic tests and vaccines; 2) M. africanum is more prevalent in HIV infected people, suggesting M. africanum behaves as a more opportunistic infection, 3) M. africanum is less likely to progress to disease in household contacts during the 2 year follow-up. These observations led Dr. de Jong to hypothesize that genetic differences relative to M. tuberculosis result in M. africanum's weakened ability to progress from infection to disease, and that this is compensated by increased persistence due to evasion of the immune response. In turn, she hypothesizes that latent infection with M. africanum provides a degree of immunization against disease with M. tuberculosis. She now proposes to test these hypotheses with studies on differences in the genome and ex vivo transcriptome, as well as immunological studies using antigens specific to M. africanum and M. tuberculosis in TB cases and their household contacts. Moreover, she plans to characterize the immune response to M. africanum and M. tuberculosis in more detail. Looking at HIV/TB co-infection, she will correlate the CD4 counts of HIV patients in the Gambia and Guinea- Bissau before and after antitubercular therapy with the mycobacterial genotype cultured from their sputum. This will demonstrate if disease with M. africanum occurs at lower CD4 counts or if it is simply more immunosuppressive. M. africanum infection provides an important model for understanding M. tuberculosis infections. Combining information from the full sequences, the genes preferentially expressed in active infection, and the immuno-epidemiologic data will likely lead to important insights into the pathogenesis of M. tuberculosis infection with relevance to enhancing our tools for the diagnosis and control of this disease. Tuberculosis is caused by any of a group of related bacteria, one of which is very common in West-Africa. The proposed research tries to explain why this bacterium, M. africanum, is more common in HIV infected people, and why a new diagnostic test does not work as well in people with this type of tuberculosis.

描述（由申请人提供）：在第一届国际研究发展奖期间，德容博士于2003年搬到冈比亚。她的目的是确定M。结核菌株特别适合于传播和空化;然而，M. africanum和M.结核病使她能够比较两个在遗传学上不同的M.肺结核综合征结果表明：1）感染者和接触者均为M。ESAT-6免疫反应迟钝，与非洲黑热病的发生发展有关 诊断测试和疫苗; 2）M. Africanum在HIV感染者中更常见，提示M. Africanum表现为机会性感染;在2年随访期间，家庭接触者中非洲人不太可能进展为疾病。这些观察使德容博士假设，相对于M。结核病导致M.非洲人从感染发展为疾病的能力减弱，这是由于逃避免疫反应而增加的持久性所补偿的。反过来，她假设M. africanum提供了一定程度的抗M.结核她现在建议通过研究基因组和体外的差异来验证这些假设。 转录组，以及免疫学研究使用抗原特异性M。africanum和M.结核病患者及其家庭接触者中的结核病。此外，她计划描述对M. africanum和M.肺结核更详细她将冈比亚和几内亚-比绍的艾滋病患者在抗结核治疗前后的CD 4计数与从他们的痰中培养的分枝杆菌基因型联系起来，研究艾滋病/结核病合并感染。这将证明如果疾病与M。如果它仅仅是免疫抑制性更强，则在较低的CD 4计数下发生。M. africanum感染为了解M.肺结核感染。结合全序列信息、活动性感染中优先表达的基因以及免疫流行病学数据，可能会对M.结核病感染与加强我们诊断和控制这种疾病的工具有关。结核病是由一组相关细菌中的任何一种引起的，其中一种在西非非常常见。这项拟议中的研究试图解释为什么这种细菌M.非洲结核病在艾滋病毒感染者中更常见，以及为什么新的诊断测试在这种类型的结核病患者中不起作用。