In Situ Bioorthogonal Conjugation of Delivered Bacteria with Gut Inhabitants for Enhancing Probiotics Colonization.

ABSTRACT: Clinical treatment efficacy of oral bacterial therapy has been largely limited by insufficient gut retention of probiotics. Here, we developed a bioorthogonal-mediated bacterial delivery strategy for enhancing probiotics colonization by modulating bacterial adhesion between probiotics and gut inhabitants. Metabolic amino acid engineering was applied to metabolically incorporate azido-decorated d-alanine into peptidoglycans of gut inhabitants, which could enable in situ bioorthogonal conjugation with dibenzocyclooctyne (DBCO)-modified probiotics. Both in vitro and in vivo studies demonstrated that the occurrence of the bioorthogonal reaction between azido- and DBCO-modified bacteria could result in obvious bacterial adhesion even in a complex physiological environment.

SUBMITTER: Song WF 

PROVIDER: S-EPMC9523781 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature