State Key Laboratory of Food Science and Technology, Nanchang University, 235 Nanjing East Road, Nanchang 330047, PR China.
Microbes Infect. 2013 May;15(5):388-98. doi: 10.1016/j.micinf.2013.02.005. Epub 2013 Feb 26.
We report our investigation of the functions of PagN in Salmonella pathogenesis and its potential as a vaccine candidate. Further investigation conducted in this study indicates that the outer membrane protein PagN is important for Salmonella adhesion/invasion of epithelial cells as well as bacterial virulence. When pagN was deleted from Salmonella enterica serovar Typhimurium (S. Typhimurium), the adhesion and invasion of HT-29 epithelial cells was significantly decreased compared with the wild type strain. Mice infected with the pagN mutant strain exhibited less pathological signs in the intestine and survived longer than the wild-type-infected mice. PagN is widely distributed and conserved among clinical isolates of different Salmonella serovars, making PagN a potential vaccine candidate for Salmonella infection. To elucidate the potential of PagN as a vaccine, we expressed and purified recombinant PagN (rPagN). When rPagN was tested in mice, it provided significant protection against Salmonella infection in vivo. In vitro, anti-PagN serum enhanced clearance of Salmonella, indicating a contribution of PagN-specific antibodies to the killing process. This correlates well with the observed protection of mice immunized with rPagN. Our preliminary results indicate more functions of PagN in S. Typhimurium virulence as well as its potential as a protective vaccine.
我们报告了 PagN 在沙门氏菌发病机制中的功能及其作为疫苗候选物的潜力的研究结果。本研究进一步表明,外膜蛋白 PagN 对于沙门氏菌黏附/侵袭上皮细胞以及细菌毒力是重要的。当从鼠伤寒沙门氏菌(S. Typhimurium)中缺失 pagN 时,与野生型菌株相比,HT-29 上皮细胞的黏附和侵袭明显减少。感染 pagN 突变株的小鼠在肠道中表现出的病理迹象较少,并且比感染野生型的小鼠存活时间更长。PagN 在不同血清型的临床分离株中广泛分布且保守,这使得 PagN 成为沙门氏菌感染的潜在疫苗候选物。为了阐明 PagN 作为疫苗的潜力,我们表达并纯化了重组 PagN(rPagN)。当 rPagN 在小鼠中进行测试时,它提供了针对沙门氏菌感染的显著体内保护。在体外,抗-PagN 血清增强了沙门氏菌的清除,表明 PagN 特异性抗体有助于杀伤过程。这与用 rPagN 免疫的小鼠观察到的保护作用很好地相关。我们的初步结果表明 PagN 在鼠伤寒沙门氏菌毒力中具有更多功能,以及作为保护性疫苗的潜力。