REGULATION OF EXPRESSION OF ADHERENCE FACTORS

建立传染性腹泻病的第一步是 入侵的病原菌附着在宿主组织上。 在 肠致病性大肠杆菌（ETEC）的情况下，这是介导的 定殖因子抗原（CFA），其通过血清学分类 类型. 在人ETEC菌株中，CFA/I、CFA/II（包括CS 1和CS2 皮利和CS 3柔性原纤维）、CFA/III和CFA/IV已被定义。 这些皮利在温度低于25 °时不表达，我们发现， 发现CS 1和CS2的表达是正调控的， 通过位于质粒的rns基因的产物在转录水平上表达。 最近，我们发现CFA/I抗原主要是阳性的， 由与rns同源的基因（cfaR）调节，但其他CFA/I菌株 没有RNS同源物。 我们未来五年的目标包括： CS 1和CS2操纵子的定义和表征，测定 Rns直接调控的基因，阐明了Rns的作用机制。 CS 1和CS2的温度调节，确定rns是否 表达这些和其它菌毛蛋白操纵子所必需的，并阐明 在没有cfaR基因的菌株中CFA/I的调节机制。 我们希望，从这项工作中收集的信息将导致更好的 了解基因表达的温度调节， 预防人类ETEC疫苗的开发策略 菌株，或可能的粘附素类似物治疗的发展。

The first step in establishment of infectious diarrheal disease is the attachment of the invading pathogenic bacteria to the host tissue. In the case of enterotoxigenic Escherichia coli (ETEC), this is mediated by colonization factor antigens (CFA) which are classified by serological type. In human ETEC strains, CFA/I, CFA/II (which includes the CS1 and CS2 pili and the CS3 flexible fibrils), CFA/III and CFA/IV have been defined. These pili are not expressed at temperatures below about 25o, and we have found that CS1 and CS2 expression is positively regulated at the transcriptional level by the product of the plasmid-located rns gene. Recently, we have found that the major CFA/I antigen is positively regulated by a gene (cfaR) homologous to rns, but that other CFA/I strains have no rns homolog. Our goals for the next five years include the definition and characterization of the CS1 and CS2 operons, determination of the gene(s) directly regulated by Rns, elucidation of the mechanism of temperature regulation of CS1 and CS2, determination of whether rns is required for expression of these and other pilin operons, and elucidation of the mechanism of regulation of CFA/I in strains that have no cfaR gene. We hope that the information gleaned from this work will lead to a better understanding of temperature regulation of gene expression and to a strategy for the development of a vaccine to protect against human ETEC strains, or possibly to development of an adhesin analog therapy.