The spread of antibiotic-resistant bacteria is a growing problem and a public health issue. In recent decades, various genetic mechanisms involved in the spread of resistance genes among bacteria have been identified. Integrons – genetic elements that acquire, exchange, and express genes embedded within gene cassettes (GC) – are one of these mechanisms. Integrons are widely distributed, especially in Gram-negative bacteria; they are carried by mobile genetic elements, plasmids, and transposons, which promote their spread within bacterial communities. Initially studied mainly in the clinical setting for their involvement in antibiotic resistance, their role in the environment is now an increasing focus of attention. The aim of this review is to provide an in-depth analysis of recent studies of antibiotic-resistance integrons in the environment, highlighting their potential involvement in antibiotic-resistance outside the clinical context. We will focus particularly on the impact of human activities (agriculture, industries, wastewater treatment, etc.).

The rapid spread of antibiotic resistance among bacterial pathogens is a serious human health threat. While a range of environments have been identified as reservoirs of antibiotic resistance genes (ARGs), we lack understanding of the origins of these ARGs and their spread from environment to clinic. This is partly due to our inability to identify the natural bacterial hosts of ARGs and the mobile genetic elements that mediate this spread, such as plasmids and integrons. Here we demonstrate that the in vivo proximity-ligation method Hi-C can reconstruct a known plasmid-host association from a wastewater community, and identify the in situ host range of ARGs, plasmids, and integrons by physically linking them to their host chromosomes. Hi-C detected both previously known and novel associations between ARGs, mobile genetic elements and host genomes, thus validating this method. We showed that IncQ plasmids and class 1 integrons had the broadest host range in this wastewater, and identified bacteria belonging to Moraxellaceae, Bacteroides, and Prevotella, and especially Aeromonadaceae as the most likely reservoirs of ARGs in this community. A better identification of the natural carriers of ARGs will aid the development of strategies to limit resistance spread to pathogens.

There is increasing evidence that human activity, and especially the resulting effluent, has a major role in the dissemination of bacterial antibiotic-resistance determinants in the environment. Hospitals are the major antibiotic consumers and thus facilitate the spread of antibiotic resistance. Questions are increasingly being raised about the management of hospital effluents, but their involvement in antibiotic-resistance dissemination has never been assessed. Integrons are a paradigm of genetic transfer between the environmental resistome and both commensal and pathogenic bacteria. In order to assess the impact of hospital activities on antibiotic-resistance dissemination in the environment, we monitored integrons and their gene cassettes in hospital effluents, and their release in the environment. We found that bacterial communities present in a hospital effluent contained a high proportion of integrons. In terms of both their gene cassette diversity and gene cassette arrays, the urban effluent and municipal wastewater treatment plant (WWTP) influent were most similar, whereas the hospital effluent and recirculation sludge exhibited very specific patterns. We found that anthropogenic activities led to the release of abundant integrons and antibiotic-resistance gene cassettes, but we observed no specific impact of hospital activities on the receiving environment. Furthermore, although the WWTP did not reduce the normalized integron copy number, it reduced the diversity of gene cassette arrays contained in the raw wastewater, underlining the effect of the biological treatment on the anthropogenic integron pool arriving at the WWTP.

Biofilms dominate microbial life, and their importance for human health and the environment can no longer be dismissed. Nevertheless many of the processes governing this form of microbial growth are still poorly understood. This includes the horizontal exchange of genetic information, which is a major driver in bacterial evolution and rapid adaptation, exemplified by the alarming spread of multi-drug resistance among pathogens mediated by plasmids. Biofilms are often considered hot spot for horizontal gene transfer, yet several studies have shown that plasmid transfer is limited to the outer layers. On the basis of results from decades of research we analyse this paradox and discuss the mechanisms by which biofilm growth can promote the initial transfer of some plasmids, but also limit further plasmid invasion into the population or community. If we want to adequately promote or combat horizontal gene spread in biofilms, we need to gain better insight into the physicochemical and biological mechanisms that control this process.