2025-09-08 コロンビア大学
Web要約 の発言:
<関連情報>
- https://www.cuimc.columbia.edu/news/supercharging-bacteria-fight-food-poisoning
- https://www.nature.com/articles/s41551-025-01453-1
- https://medibio.tiisys.com/156696/
腸内病原性腸内細菌科細菌対策のためのCRISPR関連トランスポーゼーゼを用いた精密な病原性不活性化 Precise virulence inactivation using a CRISPR-associated transposase for combating Enterobacteriaceae gut pathogens
Carlotta Ronda,Tyler Perdue,Logan Schwanz,Diego Rivera Gelsinger,Leonie Brockmann,Andrew Kaufman,Yiming Huang,Samuel H. Sternberg & Harris H. Wang
Nature Biomedical Engineering Published:18 July 2025
DOI:https://doi.org/10.1038/s41551-025-01453-1
Abstract
Targeted gene manipulation in a complex microbial community is an enabling technology for precise microbiome editing. Here we introduce BACTRINS, an in situ microbiome engineering platform designed for efficient and precise genomic insertion of a desired payload and simultaneous knockout of target genes. This system leverages conjugation-mediated delivery of CRISPR-associated transposases to achieve RNA-guided genomic integration, allowing precise insertion of a therapeutic payload while neutralizing pathogen virulence without causing cell death. When applied against an Enterobacteriaceae Shiga toxin-producing pathogen in the gut, this system delivers a CRISPR-associated transposase by bacterial conjugation for site-specific inactivation of the Shiga toxin gene and integration of a nanobody therapeutic payload to disrupt pathogen attachment. A single dose of this therapy results in high-efficiency Shiga gene inactivation and improved survival in a murine infection model of Shiga-producing pathogen. This work establishes a new type of live bacterial therapeutic capable of reducing gut infections by transforming toxigenic pathogens into commensal protectors.
