METABOLIC ALDEHYDES AS IMMUNE EFFECTORS AGAINST TUBERCULOSIS

这一提议将检验宿主衍生的醛是宿主免疫的关键组分的假设 对抗结核分枝杆菌。我们将使用细菌和小鼠遗传学，生物化学，免疫学和 细胞生物学实验来验证这一假设。我们将找出细菌突变体， 或比亲本菌株对各种醛与一氧化氮的组合更敏感，这似乎 与几种不同醛强烈协同作用以杀死细菌。这些细菌菌株的分离将 让我们测试这些途径是否有助于细菌在小鼠中的存活。我们亦会研究 从有氧糖酵解到醛脱氢酶活性的各种宿主途径，以评估 这些途径的醛产物在细菌感染控制中的作用。我们的研究结果可能最终 有助于促进一项临床试验，将FDA批准的药物用于治疗结核病， 其它疾病

This proposal will test the hypothesis that host-derived aldehydes are a critical component of host immunity against Mycobacterium tuberculosis. We will use bacterial and mouse genetics, biochemistry, immunology and cell biology experiments to test this hypothesis. We will identify bacterial mutants that are either more resistant or more sensitive than parental strains to various aldehydes in combination with nitric oxide, which appears to strongly synergize with several different aldehydes to kill bacteria. The isolation of these bacterial strains will allow us to test whether or not these pathways contribute to bacterial survival in mice. We will also investigate various host pathways from aerobic glycolysis to aldehyde dehydrogenase activity to assess the contribution of aldehyde products of these pathways in bacterial infection control. The outcome of our studies may ultimately help promote a clinical trial repurposing an FDA-approved drug for the treatment of tuberculosis and possibly other diseases.