Community-promoted antibiotic resistance genes show increased dissemination among pathogens

Antibiotic resistance is increasing among bacterial pathogens, posing one of the most severe threats to future public health. A major contributor to the increasing resistance is the dissemination of mobile antibiotic resistance genes (ARGs) among bacterial communities. These genes are ubiquitously present in various environments and are especially diverse in the human gut and wastewater. Despite this, the clinical implications of the prevalence of ARGs in these bacterial communities remain unclear. In this study, we aimed to investigate how the prevalence of ARGs in human gut and wastewater microbiomes reflects their dissemination among important bacterial pathogens. To do this, we estimated the prevalence of >30,000 ARGs, including both well-known (established) and computationally predicted (latent) genes, in >6,000 metagenomic samples. From their prevalence in the human gut and wastewater, we identified four categories of ARGs: co-promoted, human gut (HG)-promoted, wastewater (WW)- promoted, and non-promoted. Our results showed that co-promoted ARGs were by far the most promiscuous, being more frequently found across multiple bacterial phyla, and more often co-localized with broad host range conjugative elements. Co-promoted ARGs were also found to be overrepresented among genes identified in multiple pathogenic species and exhibited an overall higher genetic compatibility with both pathogens and other typical residents of the human gut and wastewater microbiomes. Taken together, our results highlight the link between the promotion of ARGs in the human gut and wastewater microbiomes and their presence in human pathogens, and, thereby, the genes’ potential risk to human health.