NanI sialidase enhances C. perfringens host cell adherence and toxin action

NanI 唾液酸酶增强产气荚膜梭菌宿主细胞粘附和毒素作用

• 批准号: 8604686
• 负责人: Jihong Li
• 金额: $ 7.66万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8604686
• 关键词: Adherence; Animals; Antibiotic Therapy; Antibiotics; Antitoxins; Bacteria; Binding; Cells; Clostridium perfringens; Clostridium perfringens epsilon toxin; Data; Development; Diarrhea; Disease; Enteral; Enterocytes; Enterotoxemia; Food Poisoning; Goals; Human; In Vitro; Infection; Influenza; Influenza A virus; Influenza B virus; Intestines; Intoxication; Lead; MDCK cell; Neuraminidase; Organism; Pathogenesis; Pilot Projects; Production; Research Project Grants; Role; Specificity; Testing; Therapeutic; Toxin; United States National Institutes of Health; Virulence; Work; base; cytotoxicity; enteritis; in vivo; inhibitor/antagonist; novel strategies; novel therapeutic intervention; pathogen; prophylactic; public health relevance

DESCRIPTION (provided by applicant): Clostridium perfringens is a major pathogen of humans and agriculturally important animals. The virulence of this bacterium is largely attributable to its ability to produce more than 15 toxins. Based upon production of four typing toxins (¿, ¿, ¿ and ?), isolates of this organism are commonly classified into five toxino-types (type A through E). The initial step of C. perfringens infections originating in the intestines is bacterial adherence to enterocytes. Our group has recently demonstrated that this adherence requires production of the C. perfringens sialidase NanI. NanI was also shown to enhance for C. perfringens strain CN3718, ETX binding and ETX-induced cytotoxicity to MDCK cells. To eventually evaluate potential C. perfrigens disease therapy aimed at interfering with bacterial adherence and toxin binding to target cells, this proposal will begin assessing whether NanI inhibitors represent potential therapeutics that might interfere with C. perfringens intestinal adherence and/or reduce toxin binding. Aim 1 of this R03 application will determine if other C. perfringens strains require NanI for this adherence. Aim 2 will test whether NanI also enhances the binding and cytotoxicity of other C. perfringens toxin besides ETX. Aim 3 studies will test the effects of sialidase inhibitors on in vitro NanI activity, toxin binding and bacterial adherence. Tis work is a pilot study that via a subsequent R01 application may lead to novel therapeutic approaches against C. perfringens diseases, similar to the use of sialidase inhibitors in the treatment of influenza caused by influenza A virus and influenza B virus.

描述（由申请人提供）：产气荚膜梭状芽胞杆菌是人类和重要农业动物的主要病原体。这种细菌的毒性很大程度上归因于它能够产生超过15种毒素。根据产生四种分型毒素（¿，¿，¿和？），该生物的分离株通常分为五种毒素类型（A型至E型）。产气荚膜原梭菌感染的最初步骤是细菌附着在肠细胞上。我们的团队最近证明，这种粘附需要产气荚膜梭菌唾液酸酶NanI的产生。NanI对产气荚膜荚膜梭菌CN3718、ETX结合和ETX诱导的MDCK细胞毒性也有增强作用。为了最终评估潜在的产气荚膜梭菌疾病治疗，目的是干扰细菌粘附和毒素与靶细胞的结合，本提案将开始评估NanI抑制剂是否代表可能干扰产气荚膜梭菌肠道粘附和/或减少毒素结合的潜在治疗方法。本R03应用的目的1将确定其他产气荚膜荚膜杆菌菌株是否需要NanI来实现这种粘附。Aim 2将测试NanI是否也增强了除ETX外其他产气荚膜荚膜菌毒素的结合和细胞毒性。目的3研究将测试