Role in virulence and protective efficacy in pigs of Salmonella enterica serovar Typhimurium secreted components identified by signature-tagged mutagenesis
Role in virulence and protective efficacy in pigs of Salmonella enterica serovar Typhimurium secreted components identified by signature-tagged mutagenesis
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DOI：
10.1099/mic.0.2006/006726-0
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发表时间：
2007-06-01
期刊：
影响因子：
2.8
通讯作者：
Stevens, Mark P.
中科院分区：
文献类型：
--
作者：
Carnell, Sonya C.;Bowen, Alison;Stevens, Mark P.
鼠伤寒沙门氏菌（S.鼠伤寒沙门氏菌（Typhimurium）是一种重要的人畜共患肠道病原体，猪是人类感染的重要宿主。利用标记转座子突变技术（STM）鉴定了S.鼠伤寒杆菌在猪肠中定植。构建了1045个S.在一式两份经口接种猪后筛选鼠伤寒沙门氏菌ST 4/74 Nal（R）。在95个不同的基因中总共鉴定了119个减毒突变，其中许多基因编码已知或推定的分泌或表面锚定分子。大量减毒突变位于沙门氏菌致病岛（SPI）-1和-2内，证实了III型分泌系统（T3 SS）-1和-2在猪肠道定殖中的重要作用。在其他致病岛和小岛，包括SPI-6编码的Saf非典型菌毛编码的基因的作用也被确定。考虑到分泌因子的作用和通过接种胞外和III型分泌蛋白质而赋予的针对其它病原体的保护作用，来自野生型S.对猪肌内接种后的鼠伤寒沙门氏菌进行了评价。免疫后诱导了针对III型分泌蛋白的血清IgG应答，并显著减少了粪便中S。与模拟接种动物相比，在感染急性期观察到鼠伤寒。用来自同基因S.鼠伤寒prgH突变体产生与用来自亲本菌株的制剂接种相当的保护水平，表明保护不依赖于T3 SS-1分泌的蛋白。这些数据为猪沙门氏菌的控制提供了有价值的信息。
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a zoonotic enteric pathogen of worldwide importance and pigs are a significant reservoir of human infection. Signature-tagged transposon mutagenesis (STM) was used to identify genes required by S. Typhimurium to colonize porcine intestines. A library of 1045 signature-tagged mutants of S. Typhimurium ST4/74 Nal(R) was screened following oral inoculation of pigs in duplicate. A total of 119 attenuating mutations were identified in 95 different genes, many of which encode known or putative secreted or surface-anchored molecules. A large number of attenuating mutations were located within Salmonella pathogenicity islands (SPI)-1 and -2, confirming important roles for type III secretion systems (T3SS)-1 and -2 in intestinal colonization of pigs. Roles for genes encoded in other pathogenicity islands and islets, including the SPI-6-encoded Saf atypical fimbriae, were also identified. Given the role of secreted factors and the protection conferred against other pathogens by vaccination with extracellular and type III secreted proteins, the efficacy of a secreted protein vaccine from wild-type S. Typhimurium following intramuscular vaccination of pigs was evaluated. Serum IgG responses against type III secreted proteins were induced following vaccination and a significant reduction in faecal excretion of S. Typhimurium was observed in the acute phase of infection compared to mock-vaccinated animals. Vaccination with secreted proteins from an isogenic S. Typhimurium prgH mutant produced comparable levels of protection to vaccination with the preparation from the parent strain, indicating that protection was not reliant on T3SS-1 secreted proteins. The data provide valuable information for the control of Salmonella in pigs.