Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage

Heike Schmitt ,Timo Röder ,Clara Amid ,Tine Hald ,Awa Aı̈dara-Kane ,Bent Petersen ,Guy Cochrane ,Josef Korbinian Vogt ,Håkan Vigre ,Rolf Sommer Kaas ,Philip Thomas Lanken Conradsen Clausen ,Mark E J Woolhouse ,Bram A D Van Bunnik ,T Zuidema ,Thomas Nordahl Petersen ,Luke Mcnally ,Oksana Lukjancenko ,Pimlapas Leekitcharoenphon ,Simon Rasmussen ,David F Nieuwenhuijse ,Ole Lund ,René S Hendriksen ,Ana Maria De Roda Husman ,Marion Koopmans ,Sünje Johanna Pamp ,Thomas Sicheritz-Pontén ,Patrick Murigu Kamau Njage ,Susanne Karlsmose Pedersen ,Jette Sejer Kjeldgaard ,Patrick Munk ,M.g.m Van De Schans ,Jorge Raul Matheu Alvarez ,Frank Møller Aarestrup

doi:10.1038/s41467-019-08853-3

Abstract

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use metagenomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.

Highlights

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult
Our findings suggest that global AMR gene diversity and abundance vary by region and that improving sanitation and health could potentially limit the global burden of AMR
An average of 0.03% of the reads were assigned to AMR genes, while on average 29%, 1%, 0.4%, and 0.2% were assigned to bacterial, protozoa, plants, and human genomic material, respectively (Supplementary Data 2)

Summary

Introduction

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Current surveillance of AMR is often focusing on a few pathogens only and mainly based on passive reporting of phenotypic laboratory results for specific pathogens isolated from human clinical infections[1,3,4,5] This procedure leads to significant time delays, often incomparable data, and a narrow pathogen spectrum not capturing all relevant AMR genes, where the major part might be present in the commensal bacterial flora of healthy individuals. Metagenomic techniques, using short-read next-generation sequencing data, benefit from the ability to quantify thousands of especially transmissible resistance genes in a single sample It can provide additional information about the presence of bacterial species, pathogens, and virulence genes and the data can be reanalyzed if novel genes of interest are identified. Pehrsson et al.[16] showed that even though changes in the bacterial composition were observed between feces and sewage, this was not the case for AMR genes

Methods

Results

Conclusion