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Journal: Military Medical Research
Article Title: Octopus-inspired engineered bacteria with a plug-and-play surface display system achieves enhanced tumor-specific colonization and antitumor immunity
doi: 10.1016/j.mmr.2026.100030
Figure Lengend Snippet: Schematic of the construction and therapeutic mechanism of the octopus-inspired triple-engineered bacteria (OITE strain) . The antitumor attenuated Salmonella typhimurium AISI strain was triple-engineered. (1) ST/SC-RGD×4 “tentacles”-Surface modification: the ST sequence was expressed within the external third loop of OmpA in the AISI strain, resulting in the AISI-ST strain. The ST protein was coexpressed with OmpA (OmpA-ST fusion protein) localized to the bacterial outer membrane. An incubation with SC-RGD×4 protein (SC-RGD×4) led to the formation of AISI-ST/SC-RGD×4 strain (AISI-ST/SC-RGD×4) through ST-SC-mediated covalent conjugation. (2) Dynamic EPS “camouflage”-Immunoactivation engineering: the AISI-H-ST strain was created by introducing the quorum-sensing (QS) promoter pLuxI to control HtrA expression into AISI-ST strain, which specifically increased HtrA-mediated extracellular polysaccharide (EPS) production to amplify bacteria-mediated immune activation. (3) Anti-PD1nanobody (PD1nb) “secretion”-Checkpoint blockade engineering: further programming of AISI-H-ST strain enabled QS-triggered anti-PD1nb secretion, generating the AISI-HP-ST strain. The incubation of AISI-HP-ST strain with SC-RGD×4 protein finally produced the OITE strain (AISI-HP-ST/SC-RGD×4). The intravenously administered OITE strain highly selectively accumulates in tumors through RGD-αvβ3 integrin interactions, with subsequent bacterial proliferation initiating two therapeutic actions: HtrA-mediated immune activation via increasing immune cells infiltration and activation, and secreted PD1nb-based blockade of PD-1/PD-L1 immunosuppressive signaling. OITE. Octopus-inspired, triple-engineered bacterium; AISI. Attenuated Salmonella Δ htrA :: luxI - VNP20009 strains; ST. SpyTag; SC. SpyCatcherΔ; RGD. Arginine-glycine-aspartic acid; HtrA. High-temperature requirement A; PD1. Programmed cell death protein 1; H. HtrA; HP. HtrA and PD1nb; AHL. N-acyl homoserine lactone; MACS. Macrophages; Teffs. Effector T cells; Tregs. Regulatory T cells.
Article Snippet: To prepare the surfaces for the strain adhesion assays, the
Techniques: Bacteria, Modification, Sequencing, Membrane, Incubation, Conjugation Assay, Control, Expressing, Activation Assay, Produced