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

Abstract

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. IMPORTANCE Different from other extensively studied mobile genetic elements (MGEs) whose discoveries were initiated decades ago (1950s–1980s), integrative and conjugative elements (ICEs), a diverse array of more recently identified elements that were formally termed in 2002, have aroused increasing concern for their crucial contribution to the dissemination of antibiotic resistance genes (ARGs). However, the comprehensive understanding on ICEs’ ARG profile across the bacterial tree of life is still blurred. Through a genomic study by comparison with two key MGEs, we, for the first time, systematically investigated the ARG profile as well as the host range of ICEs and also explored the MGE-specific potential to facilitate ARG propagation across phylogenetic barriers. These findings could serve as a theoretical foundation for risk assessment of ARGs mediated by distinct MGEs and further to optimize therapeutic strategies aimed at restraining antibiotic resistance crises.