Is ICE hot? A genomic comparative study reveals integrative and conjugative elements as “hot” vectors for the dissemination of antibiotic resistance genes

Abstract

The dissemination of antibiotic resistance genes (ARGs) driven by mobile genetic elements (MGEs), especially among pathogenic bacteria, is of increasing global concern. Different from other well-characterized MGEs, integrative and conjugative elements (ICEs) have been lacking a comprehensive understanding of their roles in ARG propagation across bacterial phylogenies. Through genomic study based on a large collection of bacterial complete genomes and further comparative analysis with two prominent MGEs to spread ARGs—conjugative plasmids and class 1 integrons, we, for the first time, demonstrated that ICEs are indeed overlooked “hot” vectors from the aspects of mobility and pathogenicity: (i) ICEs exhibited broader phylogenetic distribution among two dominant phyla with high ARG diversity and (ii) ARG-carrying ICEs were significantly enriched in potential human pathogens covering all the six “ESKAPE” species, of which some displayed typical co-occurrence patterns with ARGs and virulence factors. Moreover, this first genomic comparative study also deciphered the distinct ARG profiles harbored by these three essential MGE groups in terms of diversity and prevalence, with characteristic ARG preference to each MGE group. Overall, our findings concerning the MGE-specific performance for ARG transmission, in particular, the historically understudied ICEs, could shed light on control strategy optimization to antibiotic resistance crises.