By leveraging a self-transmissible plasmid chassis, our approach achieves three key outcomes: (1) efficient horizontal transfer of dCas9-based silencing modules across diverse pks+E. coli, (2) durable repression of clb genes without bacterial killing or mutational escape, and (3) robust suppression of DNA damage, NC101 colonization, and tumor burden in mice. Here, CLYBL is linked to neoplasm.