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

Abstract

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, we retrieved sequences and metadata from the INTEGRALL database and performed literature review. Integrons (mostly class 1) carrying ≥1 BL-encoding genes (n = 1,981) were detected in 37 bacterial genera and encoded BLs from 18 families. We identified 159 BL-encoding gene cassettes (BLGCs) representing all Ambler classes, being bla_OXA-, bla_VIM- and bla_IMP-carrying integrons the most prevalent. bla_GES, bla_BEL and most metallo-BLs were exclusively associated to 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 while wastewater was the richest environmental compartment. The frequent association of BLs and integrons suggests a significant role in beta-lactams resistance dissemination. Considering that integrons are (i) low-cost structures often associated with other mobile elements, and that (ii) often carry multiple GCs (interchangeable according to environmental stimuli), the association of BL genes with integrons should always be considered a risk factor in beta-lactam resistance spread when performing surveillance and epidemiological studies. Further studies monitoring integrons prevalence and diversity, particularly across non-clinical environments, will draw a more comprehensive picture of integron-associated beta-lactams resistance dissemination.