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Expression of Periplasmic Chaperones in Salmonella Typhimurium Reduces Its Viability In Vivo

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Abstract

The efficacy of live attenuated bacterial vectors is dependent upon the fine-tuning of a strain’s immunogenicity and its virulence. Strains are often engineered to deliver heterologous antigens, but soluble expression of recombinant proteins can be troublesome. Therefore, secretion systems or chaperone proteins are routinely used to assist in attaining high levels of functional, soluble protein production. However, the effects of chaperone expression on the virulence of attenuated bacterial vectors have not been previously reported. In anticipation of utilizing periplasmic chaperone proteins to facilitate soluble production of immunomodulatory proteins in an attenuated strain of Salmonella Typhimurium, the production of the chaperones was tested for their effect on both culture growth and bacterial persistence in mouse tissues. Although no effect on growth of the bacteria was observed in vitro, the increased expression of the periplasmic chaperones resulted in over-attenuation of the Salmonella in vivo.

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Acknowledgments

The authors are grateful to Arnold Leonard for his experimental advice and critical review of the manuscript. We thank the Minnesota Supercomputing Institute for providing licenses for software used during this research. This study was financially supported by the ASL Cancer Research Fund and ProjectStealth.org.

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Authors and Affiliations

  1. Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA

    Michael John Mertensotto, Jeremy J. Drees, Lance B. Augustin & Daniel A. Saltzman

  2. Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA

    Janet L. Schottel

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  1. Michael John Mertensotto
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  2. Jeremy J. Drees
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  3. Lance B. Augustin
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  4. Janet L. Schottel
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  5. Daniel A. Saltzman
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Correspondence to Michael John Mertensotto.

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Mertensotto, M.J., Drees, J.J., Augustin, L.B. et al. Expression of Periplasmic Chaperones in Salmonella Typhimurium Reduces Its Viability In Vivo. Curr Microbiol 70, 433–435 (2015). https://doi.org/10.1007/s00284-014-0739-9

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  • DOI: https://doi.org/10.1007/s00284-014-0739-9

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