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2020-01-07Zeitschriftenartikel DOI: 10.18452/24887
The immunogenic potential of bacterial flagella for Salmonella‐mediated tumor therapy
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.accessioned2022-06-29T14:43:30Z
dc.date.available2022-06-29T14:43:30Z
dc.date.issued2020-01-07none
dc.date.updated2020-10-05T12:18:06Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/25570
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 extracellular 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 antitumor 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.eng
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSalmonella typhimuriumeng
dc.subjecthost–pathogen interactioneng
dc.subjectflagellaeng
dc.subjectluminexeng
dc.subjectbacteria‐mediated tumor therapyeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleThe immunogenic potential of bacterial flagella for Salmonella‐mediated tumor therapynone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/25570-6
dc.identifier.doihttp://dx.doi.org/10.18452/24887
dc.type.versionpublishedVersionnone
local.edoc.pages13none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
dc.description.versionPeer Reviewednone
dc.identifier.eissn1097-0215
dcterms.bibliographicCitation.doi10.1002/ijc.32807none
dcterms.bibliographicCitation.journaltitleInternational journal of cancernone
dcterms.bibliographicCitation.volume147none
dcterms.bibliographicCitation.issue2none
dcterms.bibliographicCitation.originalpublishernameWileynone
dcterms.bibliographicCitation.originalpublisherplaceHoboken, USAnone
dcterms.bibliographicCitation.pagestart448none
dcterms.bibliographicCitation.pageend460none
bua.departmentLebenswissenschaftliche Fakultätnone

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