Regulating Bacteria–Host Interactions for Disease Intervention by Covalent Conjugation of Bacterial Surface

The interactions between bacteria and in vivo environments are critical for microorganism-host association, which plays essential roles in host immunomodulation and nutrient metabolism. Regulating the interactions of bacteria with various in vivo interfaces can vary microorganism-host relationships, offering a promising approach to intervene immune and/or metabolism disorders. However, the rationale behind the modulation of bacterial interactions with surroundings is poorly understood and methods capable of modifying bacteria to tune the crosstalk with the host have been rarely reported. Recently, considerable attention has been paid to bacterial surface modification, where bacteria can be incorporated with diverse exogenous components. Among different modification strategies, surface conjugation based on covalent chemical linkages has emerged as a key tool to design and introduce functional motifs. Particularly, surface covalent conjugation (SCC) allows for stable attachment of active components to specific sites on bacteria with molecular-level specificity and selectivity, providing a solid foundation for precisely regulating bacterial interactions with in vivo environments.