STUDIES ON THE STRUCTURE AND FUNCTION OF HEAT-LABILE TOXIN FROM BORDETELLA

博德氏菌不耐热毒素的结构和功能研究

• 批准号: 3804650
• 负责人: D L BURNS
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3804650
• 关键词: Bordetella pertussis; Brucellaceae; bacterial toxins; endotoxins; free fatty acids; guinea pigs; heat; host organism interaction; immunologic skin test; ischemia; pertussis; protein structure function; species difference; vascular smooth muscle

Heat-labile toxin (HLT) is a potent toxin produced by Bordetella species. This toxin induces tissue damage and may contribute to damage observed after infection. Only one other toxin, tracheal cytotoxin, is known to be produced by all four species in the genus Bordetella. Since the different species produce similar diseases albeit in different hosts, HLT may play an important role in the pathogenesis of the organisms. We have initiated a program to examine the structure and function of this toxin. A cell culture assay for HLT was developed. In this assay, the ability of HLT to induce contraction of vascular smooth muscle cells is measured. The results obtained by this method, which allows for detection of a little as 0.6 ng/ml of the toxin, correlated well with those obtained with in vivo assays. The ability of HLT to induce skin lesions in guinea pigs was found to be inhibited by lipids. Long-chain fatty acids were found to inhibit HLT; however, fatty alcohols, neutral lipids, phospholipids, cholesterol, and prostaglandin had no measurable effect on HLT action. These data suggest that the ability of HLT to induce skin lesions in animals may depend, in part, on the free fatty acid content of the skin layer.

热不稳定毒素（HLT）是由博德特氏菌属产生的一种强效毒素。 该毒素可诱导组织损伤，并可能导致观察到的损伤 感染后 只有另一种毒素，气管细胞毒素，已知是 由博德特氏菌属的所有四个物种产生。 由于不同 尽管不同的物种在不同的宿主中产生相似的疾病，HLT可能起作用， 在生物体的发病机制中起重要作用。 我们已开始 来检测这种毒素的结构和功能 开发了HLT的细胞培养试验。 在该测定中，测定了 测量HLT诱导血管平滑肌细胞的收缩。 的 通过这种方法获得的结果，可以检测到少量的 0.6 ng/ml的毒素，与体内获得的结果相关良好 测定。 发现HLT诱导豚鼠皮肤损伤的能力是 被脂类抑制。 发现长链脂肪酸抑制HLT; 然而，脂肪醇、中性脂质、磷脂、胆固醇和 前列腺素对HLT的作用没有可测量的影响。 这些数据表明 HLT诱导动物皮肤病变的能力可能取决于， 部分，对皮肤层的游离脂肪酸含量。