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.

Antibiotic resistance genes (ARGs) have accelerated microbial threats to human health in the last decade. Many genes can confer resistance, but evaluating the relative health risks of ARGs is complex. Factors such as the abundance, propensity for lateral transmission and ability of ARGs to be expressed in pathogens are all important. Here, an analysis at the metagenomic level from various habitats (6 types of habitats, 4572 samples) detects 2561 ARGs that collectively conferred resistance to 24 classes of antibiotics. We quantitatively evaluate the health risk to humans, defined as the risk that ARGs will confound the clinical treatment for pathogens, of these 2561 ARGs by integrating human accessibility, mobility, pathogenicity and clinical availability. Our results demonstrate that 23.78% of the ARGs pose a health risk, especially those which confer multidrug resistance. We also calculate the antibiotic resistance risks of all samples in four main habitats, and with machine learning, successfully map the antibiotic resistance threats in global marine habitats with over 75% accuracy. Our novel method for quantitatively surveilling the health risk of ARGs will help to manage one of the most important threats to human and animal health.

Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an ‘omics-based’ framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as ‘current threats’ (Rank I; 3%) - already present among pathogens - and ‘future threats’ (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 ‘current threat’ ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II (‘future threats’). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions.

SUMMARY Integrons are versatile gene acquisition systems commonly found in bacterial genomes. They are ancient elements that are a hot spot for genomic complexity, generating phenotypic diversity and shaping adaptive responses. In recent times, they have had a major role in the acquisition, expression, and dissemination of antibiotic resistance genes. Assessing the ongoing threats posed by integrons requires an understanding of their origins and evolutionary history. This review examines the functions and activities of integrons before the antibiotic era. It shows how antibiotic use selected particular integrons from among the environmental pool of these elements, such that integrons carrying resistance genes are now present in the majority of Gram-negative pathogens. Finally, it examines the potential consequences of widespread pollution with the novel integrons that have been assembled via the agency of human antibiotic use and speculates on the potential uses of integrons as platforms for biotechnology.

This review explores the evolutionary forces driving the spread of antibiotic resistance genes in microbial communities.