A model for the origin of clinical class 1 integrons.

<p>(A) Diverse chromosomal class 1 integrons that are present in environmental <i>Betaproteobacteria</i> can interact with mobile DNA elements such as transposons and plasmids in the environment. Integrons have access to a vast pool of integron gene cassettes including the <i>qacE</i> cassette that encodes a membrane efflux pump; (B) A single chromosomal integron is captured by a Tn<i>5090</i>-like transposon, to generate Tn<i>402</i>; (C) Now mobilized, the integron is free to move between a range of bacterial species. In particular, the Tn<i>402</i> transposon inserts into the mercury resistance Tn<i>501</i>-like transposon, to generate Tn<i>21</i>. Residence of this complex DNA element on a broad host range plasmid allows the integron to make its way into the human commensal flora via food-borne bacteria; (D) Once resident within the human microbiota, the integron is fixed by selection, driven by mercury and disinfectants, and after introduction of sulfonamide antibiotics, captures the <i>sul1</i> and <i>orf5</i> gene cassettes to delete part of the original <i>qacE</i> cassette; (E) Partial deletions of the <i>tni</i> module, and the collective acquisition of diverse resistance cassettes, lead to the diversity of clinical class 1 integrons that have since disseminated around the globe.