Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge.
Regulated delayed synthesis of lipopolysaccharide and enterobacterial common antigen of Salmonella Typhimurium enhances immunogenicity and cross-protective efficacy against heterologous Salmonella challenge.
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调节鼠伤寒沙门氏菌脂多糖和肠细菌共同抗原的延迟合成可增强针对异源沙门氏菌攻击的免疫原性和交叉保护功效
DOI：
10.1016/j.vaccine.2016.07.010
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发表时间：
2016-08-05
期刊：
影响因子：
5.5
通讯作者：
Kong Q
中科院分区：
文献类型：
--
作者：
Huang C;Liu Q;Luo Y;Li P;Liu Q;Kong Q
脂多糖（LPS）O-抗原和肠杆菌共同抗原（ECA）是鼠伤寒沙门氏菌表面的两种主要多糖结构。先前的研究已经证明，LPS的调节性截短增强了对来自肠道细菌的保守外膜蛋白（OMP）的交叉反应。我们推测，O-抗原和ECA的调节可能会增强对肠道细菌保守外膜蛋白的免疫应答的诱导。在这项工作中，我们靶向rfbB和rffG基因编码dTDP-葡萄糖4，6-脱氢酶，并在调节O-抗原和ECA合成中具有相同的功能。我们构建了一个突变体S496（Δ rfbB 6 Δ rffG 7 Δ pagL 73：：TT araC PBAD rfbB-3），其中rfbB基因的表达在体外生长过程中依赖于外源性提供的阿拉伯糖，并实现了LPS和ECA合成的同时紧密调控，如LPS谱和使用LPS和ECA抗血清的Western印迹所证明的。当口服给药时，S.鼠伤寒沙门氏菌S496的毒力完全减毒，但仍保留了在小鼠中定殖和传播的能力。此外，我们发现，当用致死剂量的猪霍乱沙门氏菌或肠炎沙门氏菌攻击时，与用具有Δ rfbB 6 Δ rffG 8突变的S492免疫相比，用S496口服免疫导致对来自肠道细菌的OMP的免疫应答增加，并且存活率提高。这些结果表明S.鼠伤寒沙门氏菌阿拉伯糖调节的rfbB菌株S496是一种良好的疫苗候选物，赋予针对异源沙门氏菌致死性攻击的交叉保护。
Lipopolysaccharide (LPS) O-antigen and enterobacterial common antigen (ECA) are two major polysaccharide structures on the surface of Salmonella enterica serovar Typhimurium. Previous studies have demonstrated that regulated truncation of LPS enhances the cross-reaction against conserved outer membrane proteins (OMPs) from enteric bacteria. We speculate that the regulation of both O-antigen and ECA may enhance the induction of immune responses against conserved OMPs from enteric bacteria. In this work we targeted rfbB and rffG genes which encode dTDP-glucose 4,6-dehydratases and share the same function in regulating O-antigen and ECA synthesis. We constructed a mutant, S496 (ΔrfbB6 ΔrffG7 ΔpagL73::TT araC PBAD rfbB-3), in which rfbB gene expression was dependent on exogenously supplied arabinose during in vitro growth and achieved the simultaneous tight regulation of both LPS and ECA synthesis, as demonstrated by the LPS profile and Western blotting using antisera against LPS and ECA. When administered orally, S. Typhimurium S496 was completely attenuated for virulence but still retained the capacity to colonize and disseminate in mice. In addition, we found that oral immunization with S496 resulted in increased immune responses against OMPs from enteric bacteria and enhanced survival compared with immunization with S492 possessing ΔrfbB6 ΔrffG8 mutations when challenged with lethal doses of Salmonella Choleraesuis or Salmonella Enteritidis. These results indicate that S. Typhimurium arabinose-regulated rfbB strain S496 is a good vaccine candidate, conferring cross-protection against lethal challenge with heterologous Salmonella.
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DOI：
10.4049/jimmunol.1100339
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kong Q;Six DA;Roland KL;Liu Q;Gu L;Reynolds CM;Wang X;Raetz CR;Curtiss R 3rd
通讯作者：
Curtiss R 3rd
影响因子：
6.4
作者：
HONE, D;MORONA, R;HACKETT, J
通讯作者：
HACKETT, J
影响因子：
168.9
作者：
Feasey, Nicholas A.;Dougan, Gordon;Kingsley, Robert A.;Heyderman, Robert S.;Gordon, Melita A.
通讯作者：
Gordon, Melita A.
影响因子：
3.1
作者：
Gilbreath, Jeremy J.;Dodds, Jennifer Colvocoresses;Metcalf, Eleanor S.
通讯作者：
Metcalf, Eleanor S.
影响因子：
3.2
作者：
MAROLDA, CL;VALVANO, MA
通讯作者：
VALVANO, MA