Delivery of a functional sugar-induced probiotic secretome against polymicrobial bacterial infection

The effective treatment of infection is hindered by the difficulty in simultaneously controlling bacterial burden and supporting tissue repair. Herein, a composite hydrogel system is developed by integrating a sugar-induced bacterial secretome (BS), derived from the living probiotic Escherichia coli Nissle 1917 in a state of overflow metabolism, into a collagen-based hydrogel network. Transcriptomic and untargeted metabolomic analyses reveal pronounced metabolic reprogramming under arabinose induction, leading to a reshaped extracellular secretome profile, with BS displaying stable and reproducible antibacterial activity. Functional evaluations demonstrate the in vitro broad-spectrum inhibitory activity of BS against multiple pathogenic bacteria, including methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, with antibacterial effects more likely associated with the coordinated action of multiple components rather than by a single active molecule. The incorporation of BS into the collagen hydrogel enables localized retention and sustained bioactivity while preserving favorable cytocompatibility, effectively supporting the proliferation and migration of endothelial cells and fibroblasts. In a mixed bacterial infection model, the resulting hydrogel (HAMA/BS@Col) significantly reduces the bacterial burden and enhances tissue regeneration. Overall, this work highlights BS as a functional antibacterial entity and develops a materials-based strategy that integrates infection control with regenerative support for the treatment of infection.