Functional analysis of Salmonella type III secretion system translocator protein SipC and application of vaccine development
| Project/Area Number |
18590435
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kitasato University |
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Principal Investigator |
DANBARA Hirofumi Kitasato University, School of Pharmacy, Department of Microbiology, Professor (40114558)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Nobuhiko Kitasato University, School of Pharmacy, Department of Microbiology, Associate professor (80194364)
HANEDA Takeshi Kitasato University, School of Pharmacy, Department of Microbiology, Assistant Professor (00348591)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Salmonella / virulence factors / infectious diseases / vaccine / Tyne III secretion system |
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| Research Abstract |
Type III secretion system (T3SS) is a common virulence determinant in Gram-negative bacteria and the genetic information is often clustered in pathogenicity islands or on virulence plasmids. We have analyzed the T3SS encoded by Salmonella pathogenicity island 1 (SPI-1) that is required for epithelial cell invasion of Salmonella enterica serovar Typhimurium (S. Typhimurium). SipC is a 409-amino-acid protein that is secreted by a SPI-1-encoded T3SS in S. Typhimurium. SipC is required for S. Typhimurium to translocate across the host plasma membrane a set of secreted effector proteins that function to counteract immune signaling responses and to induce host actin rearrangement. SipC contains two predicted transmembrane helices (residues 122 to 140 and 173 to 192) that are thought to insert into the host plasma membrane during translocation. To elucidate the importance of membrane insertion for SipC function, SipC proteins containing deletions and point-mutations in the transmembrane. domain were constructed. S. Typhimurium strains expressing the mutant SipC proteins were used to infect epithelial cells. Effector translocation, pore formation, and host-cell-signaling responses were studied. Introduction of deletions and point-mutations (S165P and S165A) into the transmembrane resion of SipC resulted in a nonfunctional protein that was not secreted by the type III machinery. In addition, these SipC mutant derivatives were defective for association with host cell membranes. Furthermore, a mutant Salmonella strain that expresses the SipC derivative defective in host cell membrane insertion failed to cause severe colitis in a mouse infection model. These results strongly suggest that all functions of SipC involve insertion into host membrane.
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Report
(3 results)
Research Products
(29 results)
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[Journal Article] Identification of amino acid residues of Salmonella S1yA that are critical for transcriptional regulation2007
Author(s)
Okada, N, Oi, Y, Takeda-Shitaka, M, Kanou, K, Umeyama, H, Haneda, T, Miki, T, Hosoya, S, Danbara, H
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Journal Title
Microbiology 153
Pages: 548-560
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Identification and characterization of Salmonella virulence factors required for bacterial growth in Macrophage2007
Author(s)
Yoshida, Y, Haneda, T, N, Okada, Y, Kodera, M, Ohishi, T, Maeda, H, Danbara
Organizer
The 20th Bioscience forum in Kitasato university
Place of Presentation
Ofunato, Iwate
Year and Date
2007-08-09
Description
「研究成果報告書概要(欧文)」より
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[Presentation] The alterative sigmafactor RpoN of Listeria monocytogenes contributes to its stationary growth2007
Author(s)
Okada, Y, N, Okada, S, Makino, S, Yamamoto, S, Igimi
Organizer
The 107th General meeting of American Society for Microbiology
Place of Presentation
Tronto, Canada
Year and Date
2007-05-23
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Mapping of Salmonella cell proteins by agarose 2D-electrophoresis2006
Author(s)
Haneda, T, M, Sugimoto, N, Okada, S, Shimizu, N, Nameki, Y, Kodera, M, Ohishi, T, Maeda, H, Danbara
Organizer
The 4th Clinical Proteomics Forum
Place of Presentation
Sagamihara, Kanagawa
Year and Date
2006-08-04
Description
「研究成果報告書概要(欧文)」より
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