REGULATION OF VIRULENCE FACTORS IN BORDETELLA PERTUSSIS

我们实验室的工作一直与波尔德氏菌的vir基因有关 百日咳。该基因座负责百日咳杆菌的调节。 毒力决定因素(百日咳毒素、丝状血凝素等) 对环境刺激的反应。我们最近开发出了强大的 细菌基因组分析的新物理和遗传学方法。 物理方法使我们能够比较五个B。 百日咳杆菌和1株副百日咳杆菌。令人惊讶的是，我们的结果 表明在基因组组织中可以有很大的变异 百日咳杆菌菌株之间和百日咳杆菌种之间 和副咳杆菌。新的遗传工具(具体地说，一套捐赠者 允许我们执行HFR图谱的菌株)，我们开发的 允许我们与加州大学的尼克·卡博内蒂博士合作 在巴尔的摩的马里兰州，绘制了一个参与调控的新基因 百日咳毒素和腺苷环化酶，但不是丝状血凝素。 这一发现支持了B国监管级联的概念。 百日咳，所有的毒力决定因素最终都由 VIR基因座，但可能存在其他仅涉及 对一个或几个毒力决定因素的调节。使用我们的新产品 基因工具我们已经开始系统地寻找其他基因 以不同的方式影响毒力决定因素的调节 希望确定监管中涉及的所有因素 百日咳杆菌的致病力。

Work in our laboratory has been concerned with the vir locus of Bordetella pertussis. This locus is responsible for the regulation of B. pertussis virulence determinants (pertussis toxin, filamentous hemagglutinin, etc.) in response to environmental stimuli. We have recently developed powerful new physical and genetic methods for the analysis of bacterial genomes. The physical methods have allowed us to compare the genomes of five B. pertussis and one B. parapertussis strain. Surprisingly, our results have shown that there can be a great deal of variation in genomic organization both between strains of B. pertussis and between the species B. pertussis and B. parapertussis. The new genetic tools (specifically, a set of donor strains that allow us to perform Hfr mapping) that we have developed have allowed us, in collaboration with Dr. Nick Carbonetti at the University of Maryland at Baltimore, to map a new gene involved in the regulation of pertussis toxin and adenylate cyclase, but not filamentous hemagglutinin. Such a finding lends support to the concept of a regulatory cascade in B. pertussis, where all virulence determinants are ultimately regulated by the vir locus, but where there may be other regulatory loci involved only in the regulation of one or a few virulence determinants. Using our new genetic tools we have begun a systematic search for other genes which affect the regulation of virulence determinants in a differential fashion with the hopes of defining all of the factors involved in the regulation of virulence in B. pertussis.