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 gene cassettes of unknown function (gcus) whose role and adaptive value remains unexplored. Here we show that gcus encode phage resistance systems, many of which are novel. Bacteriophage resistance integron cassettes (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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=150 SRC="FIGDIR/small/601719v4_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@965766org.highwire.dtl.DTLVardef@442763org.highwire.dtl.DTLVardef@7600d4org.highwire.dtl.DTLVardef@13068ca_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOSummary FigureC_FLOATNO 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. C_FIG