REGULATION OF EXPRESSION OF ADHERENCE FACTORS

建立传染性腹泻病的第一步是 将入侵的病原菌附着在宿主组织上。在 产肠毒素大肠杆菌(ETEC)的病例，这是由 克隆因子抗原(CFA)按血清学分类 打字。在人ETEC株中，CFA/I、CFA/II(包括CS1和CS2 PILI和CS3柔性纤维)、CFA/III和CFA/IV已被定义。 这些菌毛在低于25摄氏度的温度下不会表现出来，我们有 发现CS1和CS2的表达在 转录水平受位于质粒区的RNS基因产物的影响。 最近，我们发现主要的CFA/I抗原是阳性的。 受与RNS同源的基因(CFAR)调控，但其他CFA/I菌株 没有RNS同源基因。我们今后五年的奋斗目标包括 CS1和CS2操纵子的定义和表征、测定 对受RNS直接调控的基因(S)，阐明其作用机制 CS1和CS2的温度调节，确定RNS是否 这些和其他菌毛蛋白操纵子的表达所需的，并阐明 不含CFAR基因菌株的CFA/I调控机制。 我们希望从这项工作中收集到的信息将导致更好的 理解温度对基因表达的调节以及对 预防人类ETEC疫苗的开发策略 菌株，或可能与粘附素类似物疗法的发展有关。

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.