In Situ Bioorthogonal Conjugation of Delivered Bacteria with Gut Inhabitants for Enhancing Probiotics Colonization.
ACS Cent Sci
; 8(9): 1306-1317, 2022 Sep 28.
Article
em En
| MEDLINE
| ID: mdl-36188344
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. 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.
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MEDLINE
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En
Revista:
ACS Cent Sci
Ano de publicação:
2022
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Article