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Salmonella enterica serovar Typhimurium ruvB mutant can confer protection against salmonellosis in mice

机译:肠炎沙门氏菌血清鼠伤寒病毒ruvB突变体可对小鼠沙门氏菌病提供保护

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摘要

Salmonella enterica is an important pathogen that causes a variety of infectious diseases in animals and humans. Live attenuated vaccines generally confer better protection than killed or subunit vaccines; however, the former are limited by their inherent toxicity. We evaluated the potential of a novel candidate Salmonella vaccine strain that lacks the ruvB gene. The ruvB gene encodes a Holliday junction helicase that is required to resolve junctions that arise during the repair of non-arresting lesions after DNA replication. The deletion of this gene in Salmonella significantly impaired cell survival and proliferation within epithelial cells and macrophages. The defective virulence in ruvB mutant may be partially due to decreased expression of ssaG, a Salmonella pathogenicity island-2 gene, and increased sensitivity to hydrogen peroxide in the lack of ruvB gene. The virulence of the ruvB-deleted mutant was also greatly attenuated in BALB/c mice. The ruvB mutant conferred strong and durable immune-based protection against a challenge with a lethal dose of a virulent strain of Salmonella Typhimurium. Moreover, protective immunity was induced by a single dose of the vaccine, and the efficacy of protection was maintained for at least 6 months. These results suggest the use of the S. Typhimurium ruvB mutant as a novel vaccine
机译:肠沙门氏菌是一种重要的病原体,可引起动物和人类的多种传染病。减毒活疫苗通常比灭活或亚单位疫苗提供更好的保护;但是,前者受其固有毒性的限制。我们评估了缺少ruvB基因的新型沙门氏菌候选疫苗株的潜力。 ruvB基因编码一个霍利迪连接解旋酶,该酶是解决DNA复制后非阻滞性病变修复期间出现的连接所必需的。沙门氏菌中该基因的缺失显着损害上皮细胞和巨噬细胞内的细胞存活和增殖。 ruvB突变体中的毒力缺陷可能部分归因于ssaG(沙门氏菌致病岛2基因)的表达降低,以及缺少ruvB基因时对过氧化氢的敏感性增加。 ruvB缺失的突变体的毒性在BALB / c小鼠中也大大减弱。 ruvB突变体针对致命剂量的鼠伤寒沙门氏菌毒株提供了强大而持久的基于免疫的保护,以应对挑战。此外,单剂疫苗诱导了保护性免疫,并且保护效果至少维持了6个月。这些结果表明鼠伤寒沙门氏菌ruvB突变体作为新型疫苗的用途

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