Mobile Integrons Encode Phage Defense Systems

Abstract Integrons are bacterial genetic elements that capture, stockpile and modulate the expression of genes encoded in integron cassettes. Mobile Integrons (MI) are borne on plasmids, acting as a vehicle for hundreds of antimicrobial resistance genes among key pathogens. These elements also carry g ene c assettes of u nknown function ( gcu s) whose role and adaptive value remains unexplored. Here we show that gcu s encode phage resistance systems, many of which are novel. B acteriophage r esistance i ntegron c assettes (BRiCs) can be combined and mixed with resistance cassettes to produce multiphage or drug/phage-resistance. The fitness costs of BRiCs are variable, dependent on the genetic context, and can be modulated by changing the order of cassettes in the array. Hence, MIs act as highly mobile, low-cost defense islands. Abstract Figure Summary Figure Novel phage defense systems identified in Mobile Integrons. We confronted genes of unknown function from mobile integrons against a panel of phage. We characterized 13 Bacteriophage Resistance integron Cassettes (BRiCs) and confirmed their function in Klebsiella pneumoniae and Pseudomonas aeruginosa . Combined with other cassettes, BRiCs produce multi-phage/antibiotic resistance. Additionally, their cost can be reduced in an array.