Oral Immunization with ATP-Dependent Protease-Deficient Mutants Protects Mice against Subsequent Oral Challenge with Virulent<i>Salmonella enterica</i>Serovar Typhimurium

• Hidenori Matsui

  Laboratory of Immunoregulation, Department of Infection Control and Immunology, Kitasato Institute for Life Sciences, Kitasato University, Minato-ku, Tokyo 108-8641

• Masato Suzuki

  Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522

• Yasunori Isshiki

  Center for Basic Research, The Kitasato Institute, Minato-ku, Tokyo 108-8642

• Chie Kodama

  Laboratory of Immunoregulation, Department of Infection Control and Immunology, Kitasato Institute for Life Sciences, Kitasato University, Minato-ku, Tokyo 108-8641

• Masahiro Eguchi

  Laboratory of Immunoregulation, Department of Infection Control and Immunology, Kitasato Institute for Life Sciences, Kitasato University, Minato-ku, Tokyo 108-8641

• Yuji Kikuchi

  Laboratory of Immunoregulation, Department of Infection Control and Immunology, Kitasato Institute for Life Sciences, Kitasato University, Minato-ku, Tokyo 108-8641

• Kenji Motokawa

  Division of Research and Development, Research Center for Biologicals, The Kitasato Institute, Kitamoto, Saitama 364-0026, Japan

• Akiko Takaya

  Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522

• Toshifumi Tomoyasu

  Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522

• Tomoko Yamamoto

  Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522

抄録

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 × 10 8 CFU of the ClpXP- or Lon-deficient strain, bacteria were detected with 10 3 to 10 4 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.

収録刊行物

• Infection and Immunity

  Infection and Immunity 71 (1), 30-39, 2003-01

  American Society for Microbiology

キーワード

• Infectious Diseases
• Immunology
• Microbiology
• Parasitology

詳細情報

• CRID: 1363107369763769728
• NII論文ID: 30020830738
• DOI: 10.1128/iai.71.1.30-39.2003
• ISSN: 10985522
• ISSN: 00199567
• Web Site: https://journals.asm.org/doi/pdf/10.1128/IAI.71.1.30-39.2003
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