Abstract
Bacteria-based tumor therapy has attracted much attention due to its unique mechanism and abundant application. With the rapid development of synthetic biology, utilizing gene technology to make bacteria express therapeutic agents has greatly innovated bacterial therapy paradigms. Herein, we constructed an Escherichia coli expressing promelittin protein system based on the Trojan horse strategy, which limited the toxicity of melittin through the fusion protein during melittin expression. After targeted colonization of bacteria in tumor tissues, promelittin was activated by matrix metalloproteinase, followed by causing tumor cell death through a membrane-lytic mechanism. Additionally, the released cytolytic melittin in turn killed the maternal bacteria, eliminating safety hazards and triggering host immunity. Detailed experiments revealed that the bacteria expressing the promelittin system could significantly inhibit the proliferation and metastasis of primitive tumors in a CT26-bearing mice model. This study sheds insights into the development of bacteria-based synergistic tumor therapy.