Journal Article

Secretory delivery of recombinant proteins in attenuated Salmonella strains: potential and limitations of Type I protein transporters

Heinz P. Hahn and Bernd-Ulrich von Specht

in FEMS Immunology & Medical Microbiology

Published on behalf of Federation of Microbiological Societies

Volume 37, issue 2-3, pages 87-98
Published in print July 2003 | ISSN: 0928-8244
Published online January 2006 | e-ISSN: 1574-695X | DOI: https://dx.doi.org/10.1016/S0928-8244(03)00092-0
Secretory delivery of recombinant proteins in attenuated Salmonella strains: potential and limitations of Type I protein transporters

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Abstract

Live attenuated Salmonella strains have been extensively explored as oral delivery systems for recombinant vaccine antigens and effector proteins with immunoadjuvant and immunomodulatory potential. The feasibility of this approach was demonstrated in human vaccination trials for various antigens. However, immunization efficiencies with live vaccines are generally significantly lower compared to those monitored in parenteral immunizations with the same vaccine antigen. This is, at least partly, due to the lack of secretory expression systems, enabling large-scale extracellular delivery of vaccine and effector proteins by these strains. Because of their low complexity and the terminal location of the secretion signal in the secreted protein, Type I (ATP-binding cassette) secretion systems appear to be particularly suited for development of such recombinant extracellular expression systems. So far, the Escherichia coli hemolysin system is the only Type I secretion system, which has been adapted to recombinant protein secretion in Salmonella. However, this system has a number of disadvantages, including low secretion capacity, complex genetic regulation, and structural restriction to the secreted protein, which eventually hinder high-level in vivo delivery of recombinant vaccines and effector proteins. Thus, the development of more efficient recombinant protein secretion systems, based on Type I exporters can help to improve efficacies of live recombinant Salmonella vaccines. Type I secretion systems, mediating secretion of bacterial surface layer proteins, such as RsaA in Caulobacter crescentus, are discussed as promising candidates for improved secretory delivery systems.

Keywords: ATP-binding cassette transporter; Caulobacter crescentus; Hemolysin; Protein secretion; Salmonella; Surface layer

Journal Article.  8117 words.  Illustrated.

Subjects: Medical Microbiology and Virology ; Biotechnology ; Genetics and Genomics ; Microbiology ; Molecular and Cell Biology

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