Mobile Gene Cassettes and Integrons: Moving Antibiotic Resistance Genes in Gram-Negative Bacteria

Abstract

In Gram-negative pathogens, multiple antibiotic resistance is common and many of the known resistance genes are contained in mobile gene cassettes. Cassettes can be integrated into or deleted from their receptor elements, the integrons, or infrequently may be integrated at other locations via site-specific recombination catalysed by an integron-encoded recombinase. As a consequence, arrays of several different antibiotic resistance genes can be created. Over 40 gene cassettes and three distinct classes of integrons have been identified to date. Cassette-associated genes conferring resistance to beta-lactams, aminoglycosides, trimethoprim, chloramphenicol, streptothricin and quaternary ammonium compounds used as antiseptics and disinfectants have been found. In addition, most members of the commonest family of integrons (class 1) include a sulfonamide resistance determinant in the backbone structure. Integrons are themselves translocatable, though most are defective transposon derivatives. Integron movement allows transfer of the cassette-associated resistance genes from one replicon to another or into another active transposon which facilitates spread of integrons that are transposition defective. Horizontal transfer of the resistance genes can be achieved when an integron containing one or more such genes is incorporated into a broad-host-range plasmid. Likewise, single cassettes integrated at secondary sites in a broad-host-range plasmid can also move across species boundaries.