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Isolation of a human single-chain antibody targeting to the Gly-Asp rich region of Vibrio vulnificus RtxA toxin and characterization of the cell surface adherence property of the region
Thesis

Isolation of a human single-chain antibody targeting to the Gly-Asp rich region of Vibrio vulnificus RtxA toxin and characterization of the cell surface adherence property of the region

Hsu, Fang-Yu
Masters, 國立清華大學, 分子醫學研究所
2008

Abstract

創傷弧菌 外毒素 人源單鍊抗體
Vibrio vulnificus secretes several virulence factors causing cytopathic effects on the host cells. RtxA is a major virulence factor of this bacterium that was categorized into MARTX protein family, in which members of this family are multifunctional and autoprocessing. The MARTX proteins typically contain Gly-Asp rich regions repetitive several times in the C-terminal region. The C-terminal domain had been proposed to be involved in the translocation of the MARTX toxin into eukaryotic cells, and may act as a host cell surface adhesion factor. Nevertheless, whether the Gly-Asp-rich C-terminal region of V. vulnificus RtxA indeed binds to the host cells remains to be determined. This study is divided into two parts. In the first part, we specifically cloned, overexpressed and purified the Gly-Asp rich portion of C-terminal region of V. vulnificus RtxA (GD-repeat). The recombinant protein was then utilized as the target for screening human single-chain variable fragment (scFv) phage display library. The second part of this study aims at characterization of the cell surface adhesion property of recombinant GD-repeat, and a structure modeling web server (SwissModel) was employed to predict the molecular structure of this cloned region. One antibody (scFv-GD23C) showed binding activity to recombinant GD-repeat. In subsequent Western blot analysis, the antibody not only specifically recognized the GD-repeat, but also detected Vibrio vulnificus RtxA fragment in bacterial lysate. In the second part, the surface adhesions on HEp-2 cells of the cloned GD-repeat was demonstrated by immunofluorescence, and the result of modeling had described a special □-barrel structure of this region. The structure is similar to the C-terminal regions of other RTX proteins, suggesting this region may possess calcium-binding activity and being responsible for toxin-host cell interaction.

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