In SituBioorthogonal Conjugation of Delivered Bacteria with Gut Inhabitants for Enhancing Probiotics Colonization

Autor: Song, Wen-Fang, Yao, Wei-Qin, Chen, Qi-Wen, Zheng, Diwei, Han, Zi-Yi, Zhang, Xian-Zheng
Zdroj: ACS Central Science; September 2022, Vol. 8 Issue: 9 p1306-1317, 12p
Abstrakt: 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 situbioorthogonal conjugation with dibenzocyclooctyne (DBCO)-modified probiotics. Both in vitroand in vivostudies 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. DBCO-modified Clostridium butyricum(C. butyricum) also showed more efficient reservation in the gut and led to obvious disease relief in dextran sodium sulfate-induced colitis mice. This strategy highlights metabolically modified gut inhabitants as artificial reaction sites to bind with DBCO-decorated probiotics via bioorthogonal reactions, which shows great potential for enhancing bacterial colonization.
Databáze: Supplemental Index