Importance of mobile genetic elements for dissemination of antimicrobial resistance in metagenomic sewage samples across the world

Abstract

We are facing an ever-growing threat from increasing antimicrobial resistance (AMR) in bacteria. To mitigate this, we need a better understanding of the global spread of antimicrobial resistance genes (ARGs). ARGs are often spread among bacteria by horizontal gene transfer facilitated by mobile genetic elements (MGE). Here we use a dataset consisting of 677 metagenomic sequenced sewage samples from 97 countries or regions to study how MGEs are geographically distributed and how they disseminate ARGs worldwide. The ARGs, MGEs, and bacterial abundance were calculated by reference-based read mapping. We found systematic differences in the abundance of MGEs and ARGs, where some elements were prevalent on all continents while others had higher abundance in separate geographic areas. Different MGEs tended to be localized to temperate or tropical climate zones, while different ARGs tended to separate according to continents. This suggests that the climate is an important factor influencing the local flora of MGEs. MGEs were also found to be more geographically confined than ARGs. We identified several integrated MGEs whose abundance correlated with the abundance of ARGs and bacterial genera, indicating the ability to mobilize and disseminate these genes. Some MGEs seemed to be more able to mobilize ARGs and spread to more bacterial species. The host ranges of MGEs seemed to differ between elements, where most were associated with bacteria of the same family. We believe that our method could be used to investigate the population dynamics of MGEs in complex bacterial populations.