bims-livmat 2026-02-15 papers

on Living materials

Issue of 2026–02–15
two papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien

Surface decoration of bacteria generates robust living therapeutics for improved ulcerative colitis therapy.
Dual-Key Genetic Circuit Enables Stable and Self-Regulated Engineered Bacteria for the Treatment of Ulcerative Colitis.

Commun Biol. 2026 Feb 13.

Surface decoration of bacteria generates robust living therapeutics for improved ulcerative colitis therapy.

Junyu Liu, Zhihao Fang, Xiaobin Li, Xiaopeng Zhang, Yun Chen, Fujia Kou, Long Huang, Huanxian Yang, Yilin Zheng, Yuqing Huang, Yi Wang, Xueqing Qiu, Jun Ge, Yong Qian, Xin-Hui Xing, Can Yang Zhang.

Oral probiotics have shown great potential in treating ulcerative colitis (UC). However, gastrointestinal obstacles substantially inactivate probiotics, impeding delivery and colonization in the colon. Here, we developed robust oral living therapeutics with high colon-accumulating effect via surface decoration of probiotic (Escherichia coli Nissle 1917, EcN) using a layer-by-layer approach. Calcium ions and carboxymethyl-modified lignin (CML) were sequentially coated on EcN to generate an acid-resistant and colitis microenvironment-responsive system (CML@EcN). After oral administration in a male C57BL/6 N mouse model, EcN were specifically delivered to the site of colitis and successfully colonized. The CML@EcN notably alleviated colitis by modulating immune dysfunction, reshaping gut microbiota (GM), and repairing the intestinal barrier. The delivery mechanism was explored based on experiments and mathematical models. Interestingly, this engineering approach can be further used to decorate other bacteria. Consequently, the robust CML@EcN shows high colon-targeting delivery efficacy and great potential in UC therapy.

DOI: https://doi.org/10.1038/s42003-026-09732-6
Adv Sci (Weinh). 2026 Feb 13. e20434

Dual-Key Genetic Circuit Enables Stable and Self-Regulated Engineered Bacteria for the Treatment of Ulcerative Colitis.

Shuaijie Ding, Biao Yang, Xinyu Li, Yi Wang, Chunyu Huang, Wenfei Dong, Wei Xie.

  Engineered bacteria offer a promising therapeutic platform but often display plasmid instability and antibiotic dependence. A synthetic dual-key genetic circuit is established in Escherichia coli Nissle 1917 (EcN) by deleting both asd and thyA genes, generating an auxotrophic chassis that requires dual-plasmid complementation for survival. The "lysis module" restores asd function and incorporates a quorum-sensing system for self-regulated lysis and controlled protein release ("One Key"). By contrast, the "expression module" complements thyA and co-delivers an interleukin-2 (IL-2) mutant and the membrane protein Amuc_1100 to modulate immune balance and repair the intestinal barrier ("Dual Keys"). This dual-key design enabled antibiotic-free plasmid stability, precise population control, and sustained therapeutic protein secretion. Oral administration of the engineered strain significantly alleviated colitis in mice by enhancing regulatory T-cell expansion, restoring epithelial integrity, and reshaping the gut microbiota. This modular system provides a safe, stable, and programmable strategy for live bacterial therapy against immune and mucosal diseases.

Keywords:  engineered bacteria; genetic circuit; quorum sensing; ulcerative colitis

DOI:  https://doi.org/10.1002/advs.202520434