Oral immunization with ATP-dependent protease-deficient mutants protects mice against subsequent oral challenge with virulent Salmonella enterica serovar Typhimurium
Oral immunization with ATP-dependent protease-deficient mutants protects mice against subsequent oral challenge with virulent Salmonella enterica serovar Typhimurium
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DOI：
10.1128/iai.71.1.30-39.2003
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发表时间：
2003-01-01
影响因子：
3.1
通讯作者：
Yamamoto, T
中科院分区：
文献类型：
--
作者：
Matsui, H;Suzuki, M;Yamamoto, T
我们通过使用具有ClpXP或Lon蛋白酶破坏的肠道沙门氏菌鼠伤寒血清型突变体对小鼠进行感染研究，评估了具有应激反应蛋白酶基因缺失的突变体作为抗沙门氏菌感染的活口服疫苗菌株的候选物的功效。在体外，ClpXP蛋白酶调节鞭毛合成，并且ClpXP缺陷型突变菌株表现出超鞭毛细菌细胞（T. Tomoyasu等人，J. Bacteriol. 184：645-653，2002）。另一方面，Lon蛋白酶负调节侵入上皮细胞的功效和侵入基因的表达（A. Takaya等人，J. Bacteriol. 184：224-232，2002）。当5周龄BALB/c小鼠经口给予5 × 108 CFU ClpXP或Lon缺陷型菌株时，接种后1周，在脾脏、肠系膜淋巴结、派伊尔集合淋巴结和盲肠中检测到103至104 CFU的细菌，然后细菌在每个组织中逐渐减少。在第4周检测到脂多糖特异性免疫球蛋白G（IgG）和分泌伊加的显著增加，并分别在血清和胆汁中接种后至少维持至第12周。用ClpXP-或Lon-缺陷株免疫保护小鼠免受血清型Typhimurium强毒株的口服攻击。攻毒后5天，攻毒和免疫的无毒沙门氏菌均从脾脏、肠系膜淋巴结、派伊尔集合淋巴结甚至盲肠中完全清除。这些数据表明，具有ATP依赖性蛋白酶ClpXP或Lon破坏的沙门氏菌可用于开发活疫苗菌株。
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 Typhimuriurn 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 X 10(8) 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 Typhimuriurn 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.