Bridge recombinase enables versatile rewriting of bacterial genomes

2026 · doi:10.64898/2026.04.29.721476
preprint OA: closed
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The paper studied whether bridge recombinase, using a bridge RNA (bRNA), can enable versatile, programmable genome editing across diverse bacteria, aiming to expand tools for microbiome rewriting. In Escherichia coli, the authors report large-scale genome operations including 142 kb insertions at over 90% efficiency, 2.3 Mb inversions, and ~50 kb excisions, and they extend editing with a single ortholog across isolates spanning five bacterial phyla from human gut communities. They address technical limitations including cross-reactivity between co-expressed bRNAs by implementing search-and-replace TRADE editing, and they demonstrate capture and interphylum transfer of chromosomal pathways for programmable horizontal gene transfer. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

Bacteria drive crucial processes across ecosystems and impact human health, yet tools to rewrite microbiomes remain limited. Here, we show that bridge recombinase enables versatile and programmable genome editing across the bacterial tree of life. In Escherichia coli , we achieved 142 kb insertions at >90% efficiency, megabase-scale inversions (2.3 Mb), and pathway-scale 50 kb excisions. With a single ortholog and bridge RNA (bRNA), we edited bacterial isolates spanning five phyla and diverse members of two human gut communities. We overcame cross-reactivity between co-expressed bRNAs to establish search-and-replace Targetable Recombinase Assisted DNA Exchange (TRADE) editing and demonstrated capture and interphylum transfer of chromosomal pathways, enabling programmable horizontal gene transfer. These advances establish bridge recombinase as a foundation for reprogramming gene flow in complex microbial communities.
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Abstract Bacteria drive crucial processes across ecosystems and impact human health, yet tools to rewrite microbiomes remain limited. Here, we show that bridge recombinase enables versatile and programmable genome editing across the bacterial tree of life. In Escherichia coli, we achieved 142 kb insertions at >90% efficiency, megabase-scale inversions (2.3 Mb), and pathway-scale 50 kb excisions. With a single ortholog and bridge RNA (bRNA), we edited bacterial isolates spanning five phyla and diverse members of two human gut communities. We overcame cross-reactivity between co-expressed bRNAs to establish search-and-replace Targetable Recombinase Assisted DNA Exchange (TRADE) editing and demonstrated capture and interphylum transfer of chromosomal pathways, enabling programmable horizontal gene transfer. These advances establish bridge recombinase as a foundation for reprogramming gene flow in complex microbial communities. Competing Interest Statement The Regents of the University of California have issued a US patent application on which the authors are inventors related to this work. No other authors declare any conflicts of interest. Footnotes Revised to include updated in-text references for figures, supplementary figures, and tables; minor figure and text changes; and new author ORCIDs.

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