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Plasmid-encoded type IV-A CRISPR-Cas systems lack an acquisition module, feature a DinG helicase instead of a nuclease, and form ribonucleoprotein complexes of unknown biological functions. Type IV-A3 systems are carried by conjugative plasmids that often harbor antibiotic-resistance genes and their CRISPR array contents suggest a role in mediating inter-plasmid conflicts, but this function remains unexplored. Here, we demonstrate that a plasmid-encoded type IV-A3 system co-opts the type I-E adaptation machinery from its host, Klebsiella pneumoniae (K. pneumoniae), to update its CRISPR array. Furthermore, we reveal that robust interference of conjugative plasmids and phages is elicited through CRISPR RNA-dependent transcriptional repression. By silencing plasmid core functions, type IV-A3 impacts the horizontal transfer and stability of targeted plasmids, supporting its role in plasmid competition. Our findings shed light on the mechanisms and ecological function of type IV-A3 systems and demonstrate their practical efficacy for countering antibiotic resistance in clinically relevant strains. [Display omitted] • Type IV-A3 CRISPR-Cas acquires spacers using host I-E adaptation machinery • Plasmid-plasmid conflicts involve silencing of plasmid core functions by type IV-A3 • DinG helicase is required for repression once transcription has initiated • Type IV-A3 can be programmed as a tool to re-sensitize bacteria to antibiotics Benz and Camara-Wilpert et al. reveal that plasmid-encoded type IV-A3 CRISPR-Cas systems rely on host I-E adaptation machinery to acquire spacers and mediate inter-plasmid competition via DinG helicase-assisted transcriptional interference. By repurposing type IV-A3 as a programmable tool, clinical strains can be re-sensitized to antibiotics, offering promising approaches to tackle antibiotic resistance. [ABSTRACT FROM AUTHOR]