Integrons are key players in the spread of beta-lactamase-encoding genes
Rafael D.S. Tavares, Marta Tacão, Isabel Henriques
Abstract
• bla genes from 18 families were detected as gene cassettes. • bla GES , bla BEL and class B1 bla genes were exclusively associated to integrons. • bla genes from 13 families were identified downstream of ISCR1 in complex integrons. • Most of the bla variants identified encoded carbapenemases. 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 IS CR1 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.