Using the class 1 integron-integrase gene as a proxy for anthropogenic pollution

Abstract

Around all human activity, there are zones of pollution with pesticides, heavy metals, pharmaceuticals, personal care products and the microorganisms associated with human waste streams and agriculture. This diversity of pollutants, whose concentration varies spatially and temporally, is a major challenge for monitoring. Here, we suggest that the relative abundance of the clinical class 1 integron-integrase gene, intI1, is a good proxy for pollution because: (1) intI1 is linked to genes conferring resistance to antibiotics, disinfectants and heavy metals; (2) it is found in a wide variety of pathogenic and nonpathogenic bacteria; (3) its abundance can change rapidly because its host cells can have rapid generation times and it can move between bacteria by horizontal gene transfer; and (4) a single DNA sequence variant of intI1 is now found on a wide diversity of xenogenetic elements, these being complex mosaic DNA elements fixed through the agency of human selection. Here we review the literature examining the relationship between anthropogenic impacts and the abundance of intI1, and outline an approach by which intI1 could serve as a proxy for anthropogenic pollution.

Figure 1

Integron structure and function. Integrons consist of a gene for an integron-integrase (intI) that catalyses recombination between the attC site of circular gene cassettes and the attendant integron recombination site, attI. This activity results in the sequential insertion of multiple, different cassettes to form a tandem cassette array that, in some cases, might contain hundreds of different genes. Inserted genes are expressed by an integron-encoded promoter, Pc.

Figure 2

The recent evolutionary origin of the clinical class 1 integron and its incorporation into diverse xenogenetic elements. The raw materials for the assembly of the complex mosaic DNA elements that now carry the clinical intI1 were all present in the environmental resistome. A single sequence variant from the diverse pool of class 1 integrons in natural environments was captured by a Tn402 transposon, thus forming a Tn402–intI1 hybrid, and giving the integron greater mobility. This hybrid integron, in total, has captured at least 130 different gene cassettes encoding resistance to diverse antibiotics. At the same time, the Tn402 portion of the hybrid element targeted the res sites of plasmids, transposing the whole hybrid molecule into a diverse collection of plasmids. This, in turn, promoted movement of clinical intI1 between different bacterial species by conjugation of those plasmids. Human selection events have also independently fixed the acquisition of diverse resistance genes onto the collection of plasmids invaded by the hybrid integron. These independent acquisitions resulted in the accumulation of genes for resistance to metals, antibiotics, disinfectants and other compounds, along with other genetic elements such as insertion sequences and transposons. As a result, a single molecular species (the clinical intI1 sequence variant) has become associated with an ever expanding and diverse set of plasmids, transposons and resistance genes. These mosaic elements can be thought of as xenogenetic, in the sense that they owe their current structures and abundance to human activity.