Sedentary chromosomal integrons as biobanks of bacterial antiphage defense systems

Abstract

Integrons are genetic systems that drive bacterial adaptation by acquiring, expressing, and shuffling gene cassettes. While mobile integrons are well known for spreading antibiotic resistance genes, the functions of the hundreds of cassettes carried by sedentary integrons remain largely unexplored. We show that many of these cassettes encode small variants of known antiphage systems that favor their inclusion in the integron. We also demonstrate that nearly 10% of the integron cassettes in the pandemic Vibrio cholerae strain encode novel antiphage functions. Most of these novel systems have little or no similarity to previously known ones, with several providing defense through cell lysis or growth arrest. Our work highlights the stabilization and prevalence of small antiphage systems within integrons, making them an untapped biobank of defense mechanisms.