Efficiency of conditionally attenuated Salmonella enterica serovar typhimurium in bacterium-mediated tumor therapy

Michael Frahm, Sebastian Felgner, Dino Kocijancic, Manfred Rohde, Michael Hensel, Iii Roy Curtiss, Marc Erhardt, Siegfried Weiss

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Increasing numbers of cancer cases generate a great urge for new treatment options. Applying bacteria like Salmonella enterica serovar Typhimurium for cancer therapy represents an intensively explored option. These bacteria have been shown not only to colonize solid tumors but also to exhibit an intrinsic antitumor effect. In addition, they could serve as tumortargeting vectors for therapeutic molecules. However, the pathogenic S. Typhimurium strains used for tumor therapy need to be attenuated for safe application. Here, lipopolysaccharide (LPS) deletion mutants (ΔrfaL, ΔrfaG, ΔrfaH, ΔrfaD, ΔrfaP, and ΔmsbB mutants) of Salmonella were investigated for efficiency in tumor therapy. Of such variants, the ΔrfaD and ΔrfaG deep rough mutants exhibited the best tumor specificity and lowest pathogenicity. However, the intrinsic antitumor effect was found to be weak. To overcome this limitation, conditional attenuation was tested by complementing the mutants with an inducible arabinose promoter. The chromosomal integration of the respective LPS biosynthesis genes into the araBAD locus exhibited the best balance of attenuation and therapeutic benefit. Thus, the present study establishes a basis for the development of an applicably cancer therapeutic bacterium.

Original languageEnglish (US)
Article numbere00254-15
Pages (from-to)1-11
Number of pages11
JournalmBio
Volume6
Issue number2
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Virology

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    Frahm, M., Felgner, S., Kocijancic, D., Rohde, M., Hensel, M., Curtiss, I. R., Erhardt, M., & Weiss, S. (2015). Efficiency of conditionally attenuated Salmonella enterica serovar typhimurium in bacterium-mediated tumor therapy. mBio, 6(2), 1-11. [e00254-15]. https://doi.org/10.1128/mBio.00254-15