RT Journal Article T1 Mobile integrons encode phage defense systems A1 Kieffer, Nicolas A1 Hipólito Carrillo de Albornoz, Alberto A1 Ortiz Miravalles, Laura A1 Blanco Torres, Paula A1 Delobelle, Thomas A1 Vizuete, Patricia A1 Ojeda, Francisco Manuel A1 Jové, Thomas A1 Jurenas, Dukas A1 García Quintanilla, Meritxell A1 Carvalho, André A1 Domingo Calap, Pilar A1 Escudero García-Calderón, José Antonio AB Integrons are bacterial genetic elements that capture, stockpile,and modulate the expression of genes encoded in integroncassettes. Mobile integrons (MIs) are borne on plasmids, actingas a vehicle for hundreds of antimicrobial resistance genesamong key pathogens. These elements also carry genecassettes of unknown function (gcus) whose role and adaptivevalue remain unexplored. In this work, we show that gcusencode phage resistance systems, many of which are newlydiscovered. Bacteriophage resistance integron cassettes(BRiCs) can be combined and mixed with resistance cassettesto produce multiphage or drug and phage resistance. Thefitness costs of BRiCs are variable and dependent on thegenetic context and can be modulated by changing the order ofcassettes in the array. Hence, MIs act as highly mobile, low-costdefense islands. PB American Association for the Advancement of Science SN 0036-8075 YR 2025 FD 2025 LK https://hdl.handle.net/20.500.14352/120482 UL https://hdl.handle.net/20.500.14352/120482 LA eng NO Kieffer, N., Hipólito, A., Ortiz-Miravalles, L., Blanco, P., Delobelle, T., Vizuete, P., Ojeda, F. M., Jové, T., Jurenas, D., García-Quintanilla, M., Carvalho, A., Domingo-Calap, P., & Escudero, J. A. (2025). Mobile integrons encode phage defense systems. Science (New York, N.Y.), 388(6747), eads0915. https://doi.org/10.1126/science.ads0915 NO Author contributions: Conceptualization: J.A.E.; Investigation: N.K., A.H., L.O.M., P.B., T.D., P.V., F.M.O., T.J., M.G.-Q., A.C., P.D.-C.; Funding acquisition: J.A.E.; Project administration: J.A.E.; Supervision: M.G.-Q., P.D.-C., J.A.E.; Writing — original draft: N.K., A.H., J.A.E.; Writing — review & editing: N.K., A.H., D.J., P.D.-C., M.G.-Q., J.A.E NO European Commission NO Universidad Complutense NO Ministerio de Ciencia, Innovación y Universidades (España) NO Instituto de Salud Carlos III DS Docta Complutense RD 20 jul 2025