Efficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy.

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Hdl Handle:
http://hdl.handle.net/10033/550325
Title:
Efficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy.
Authors:
Frahm, Michael; Felgner, Sebastian; Kocijancic, Dino; Rohde, Manfred ( 0000-0003-0522-3580 ) ; Hensel, Michael; Curtiss, Roy; Erhardt, Marc; Weiss, Siegfried
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 tumor-targeting 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.
Affiliation:
Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Efficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy. 2015, 6 (2): MBio
Journal:
mBio
Issue Date:
2015
URI:
http://hdl.handle.net/10033/550325
DOI:
10.1128/mBio.00254-15
PubMed ID:
25873375
Type:
Article
Language:
en
ISSN:
2150-7511
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorFrahm, Michaelen
dc.contributor.authorFelgner, Sebastianen
dc.contributor.authorKocijancic, Dinoen
dc.contributor.authorRohde, Manfreden
dc.contributor.authorHensel, Michaelen
dc.contributor.authorCurtiss, Royen
dc.contributor.authorErhardt, Marcen
dc.contributor.authorWeiss, Siegfrieden
dc.date.accessioned2015-04-20T12:27:39Zen
dc.date.available2015-04-20T12:27:39Zen
dc.date.issued2015en
dc.identifier.citationEfficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy. 2015, 6 (2): MBioen
dc.identifier.issn2150-7511en
dc.identifier.pmid25873375en
dc.identifier.doi10.1128/mBio.00254-15en
dc.identifier.urihttp://hdl.handle.net/10033/550325en
dc.description.abstractIncreasing 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 tumor-targeting 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.en
dc.language.isoenen
dc.titleEfficiency of Conditionally Attenuated Salmonella enterica Serovar Typhimurium in Bacterium-Mediated Tumor Therapy.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalmBioen

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