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首页> 外文期刊>Infection and immunity >Oral Immunization with ATP-Dependent Protease-Deficient Mutants Protects Mice against Subsequent Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium
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Oral Immunization with ATP-Dependent Protease-Deficient Mutants Protects Mice against Subsequent Oral Challenge with Virulent Salmonella enterica Serovar Typhimurium

机译：ATP依赖性蛋白酶缺陷型突变体的口服免疫可保护小鼠免受随后的肠炎沙门氏菌血清型鼠伤寒沙门氏菌的口服攻击。

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We evaluated the efficacy of mutants with a deletion of the stress response protease gene as candidates for live oral vaccine strains against Salmonella infection through infection studies with mice by using a Salmonella enterica serovar Typhimurium mutant with a disruption of the ClpXP or Lon protease. In vitro, the ClpXP protease regulates flagellum synthesis and the ClpXP-deficient mutant strain exhibits hyperflagellated bacterial cells (T. Tomoyasu et al., J. Bacteriol. >184:645-653, 2002). On the other hand, the Lon protease negatively regulates the efficacy of invading epithelial cells and the expression of invasion genes (A. Takaya et al., J. Bacteriol. >184:224-232, 2002). When 5-week-old BALB/c mice were orally administered 5 × 108 CFU of the ClpXP- or Lon-deficient strain, bacteria were detected with 103 to 104 CFU in the spleen, mesenteric lymph nodes, Peyer's patches, and cecum 1 week after inoculation and the bacteria then decreased gradually in each tissue. Significant increases of lipopolysaccharide-specific immunoglobulin G (IgG) and secretory IgA were detected at week 4 and maintained until at least week 12 after inoculation in serum and bile, respectively. Immunization with the ClpXP- or Lon-deficient strain protected mice against oral challenge with the serovar Typhimurium virulent strain. Both the challenged virulent and immunized avirulent salmonellae were completely cleared from the spleen, mesenteric lymph nodes, Peyer's patches, and even cecum 5 days after the challenge. These data indicate that Salmonella with a disruption of the ATP-dependent protease ClpXP or Lon can be useful in developing a live vaccine strain.
机译：通过使用鼠伤寒沙门氏菌的小鼠感染研究，我们评估了缺失应激反应蛋白酶基因的突变体作为口服活疫苗株抗沙门氏菌感染的候选药物的功效。鼠伤寒突变体，具有ClpXP或Lon蛋白酶的破坏。在体外，ClpXP蛋白酶调节鞭毛的合成，而缺乏ClpXP的突变菌株则表现出超鞭毛的细菌细胞（T. Tomoyasu等人，J。Bacteriol。> 184： 645-653，2002）。另一方面，Lon蛋白酶负面地调节侵袭上皮细胞的功效和侵袭基因的表达（A.Takaya等人，J.Bacteriol。> 184： 224-232，2002）。当对5周龄的BALB / c小鼠口服ClpXP或Lon缺陷株5×10 8 CFU时，细菌检出率为10 3 至10接种后1周，脾脏，肠系膜淋巴结，淋巴集结和盲肠中的 4 CFU，然后每个组织中的细菌逐渐减少。在接种血清和胆汁后第4周检测到脂多糖特异性免疫球蛋白G（IgG）和分泌型IgA显着增加，并保持至至少第12周。 ClpXP或Lon缺陷株的免疫可以保护小鼠免受鼠伤寒鼠伤寒毒株的口服攻击。攻击后5天，已从脾脏，肠系膜淋巴结，派伊尔氏淋巴结甚至盲肠完全清除了受攻击的有毒力和免疫力的无毒沙门氏菌。这些数据表明破坏了ATP依赖的蛋白酶ClpXP或Lon的沙门氏菌可用于开发活疫苗株。

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