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dc.contributor.authorFelgner, Sebastian
dc.contributor.authorSpöring, Imke
dc.contributor.authorPawar, Vinay
dc.contributor.authorKocijancic, Dino
dc.contributor.authorPreusse, Matthias
dc.contributor.authorFalk, Christine
dc.contributor.authorRohde, Manfred
dc.contributor.authorHäussler, Susanne
dc.contributor.authorWeiss, Siegfried
dc.contributor.authorErhardt, Marc
dc.date.accessioned2020-01-06T14:38:24Z
dc.date.available2020-01-06T14:38:24Z
dc.date.issued2019-11-21
dc.date.submitted2019-11-21
dc.identifier.citationInt J Cancer. 2019 Nov 21. doi: 10.1002/ijc.32807.en_US
dc.identifier.issn1097-0215
dc.identifier.pmid31755108
dc.identifier.doi10.1002/ijc.32807
dc.identifier.urihttp://hdl.handle.net/10033/622064
dc.description.abstractGenetically engineered Salmonella Typhimurium are potent vectors for prophylactic and therapeutic measures against pathogens as well as cancer. This is based on the potent adjuvanticity that supports strong immune responses. The physiology of Salmonella is well understood. It simplifies engineering of both enhanced immune‐stimulatory properties as well as safety features, thus, resulting in an appropriate balance between attenuation and efficacy for clinical applications. A major virulence factor of Salmonella is the flagellum. It is also a strong pathogen‐associated molecular pattern recognized by extra‐ and intracellular receptors of immune cells of the host. At the same time, it represents a serious metabolic burden. Accordingly, the bacteria evolved tight regulatory mechanisms that control flagella synthesis in vivo. Here, we systematically investigated the immunogenicity and adjuvant properties of various flagella mutants of Salmonella in vitro and in a mouse cancer model in vivo. We found that mutants lacking the flagellum‐specific ATPase FliHIJ or the inner membrane ring FliF displayed the greatest stimulatory capacity and strongest anti‐tumor effects, while remaining safe in vivo. Scanning electron microscopy revealed the presence of outer membrane vesicles in the ΔfliF and ΔfliHIJ mutants. Finally, the combination of the ΔfliF and ΔfliHIJ mutations with our previously described attenuated and immunogenic background strain SF102 displayed strong efficacy against the highly resistant cancer cell line RenCa. We thus conclude that manipulating flagella biosynthesis has great potential for the construction of highly efficacious and versatile Salmonella vector strains.en_US
dc.language.isoenen_US
dc.publisherWiley-Blackwellen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectSalmonella Typhimuriumen_US
dc.subjectbacteria-mediated tumor therapyen_US
dc.subjectflagellaen_US
dc.subjecthost-pathogen interactionen_US
dc.subjectluminexen_US
dc.titleThe immunogenic potential of bacterial flagella for Salmonella-mediated tumor therapy.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalInternational Journal of Canceren_US
refterms.dateFOA2020-01-06T14:38:24Z
dc.source.journaltitleInternational journal of cancer


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