Integrons are key players in the spread of beta-lactamase-encoding genes

Integrons mediate the acquisition and expression of gene cassettes (GCs). The production of beta-lactamases (BLs) is the most relevant mechanism of beta-lactams resistance. To explore the role of integrons in BL genes dissemination, sequences and metadata were retrieved from the INTEGRALL database and a literature review performed. Integrons (mostly class 1) carrying ≥1 BL-encoding genes (n = 1981) were detected in 37 bacterial genera and encoded BLs from 18 families. A total of 159 BL-encoding gene cassettes (BLGCs) were identified, representing all Ambler classes, with bla_OXA-, bla_VIM- and bla_IMP-carrying integrons the most prevalent. bla_GES, bla_BEL and most metallo-BLs were exclusively associated with integrons. BL genes from 13 families were identified as genes captured by ISCR1 in complex integrons (n = 234), namely bla_NDM, bla_CTX-M and bla_TEM. Frequently co-detected GCs encoded resistance to all major classes of antibiotics, namely aminoglycosides, phenicols and trimethoprim. Most BLGCs encoded resistance to carbapenems (n = 90) and Pseudomonas aeruginosa was the most frequent host. Most bla-carrying integrons were from clinical contexts and wastewater was the richest environmental compartment. The frequent association of BLs and integrons indicates a significant role in dissemination of beta-lactams resistance. Considering that integrons are (i) low-cost structures often associated with other mobile elements, and (ii) often carry multiple GCs (interchangeable according to environmental stimuli), the association of BL genes with integrons should always be considered a risk factor for the spread of beta-lactam resistance when performing surveillance and epidemiological studies. Further studies monitoring prevalence and diversity of integrons, particularly across non-clinical environments, will draw a more comprehensive picture of integron-associated dissemination of beta-lactams resistance.