Controlling intracellular protein delivery, tumor colonization and tissue distribution using flhDC in clinically relevant ΔsseJ Salmonella.
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ABSTRACT: Effectively targeting intracellular pathways in cancers requires a system that specifically delivers to tumors and internalizes into cancer cells. To achieve this goal, we developed intracellular-delivering (ID) Salmonella with controllable expression of flhDC to regulate flagella production and cell invasion. We hypothesized that controlling flhDC would overcome the poor colonization seen in prior clinical trials. To test this hypothesis, we incorporated the aspirin-responsive Psal promoter and tuned flhDC expression with ssra degradation tags. In tumor-bearing mice, controlling flhDC increased protein release, tissue dispersion, and tumor colonization more than 10 million times. We discovered that inducing flhDC increases escape from intracellular vacuoles; however, deleting sseJ prevent
SUBMITTER: Raman V
PROVIDER: S-EPMC11852948 | biostudies-literature | 2025 Feb
REPOSITORIES: biostudies-literature
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