Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage
Authors: Hendriksen Rene S. , Munk Patrick , Njage Patrick , van Bunnik Bram , McNally Luke , Lukjancenko Oksana , Röder Timo , Nieuwenhuijse David , Pedersen Susanne Karlsmose , Kjeldgaard Jette , Kaas Rolf S. , Clausen Philip Thomas Lanken Conradsen , Vogt Josef Korbinian , Leekitcharoenphon Pimlapas , van de Schans Milou G. M. , Zuidema Tina , de Roda Husman Ana Maria , Rasmussen Simon , Petersen Bent ,   The Global Sewage Surveillance project consortium, Bego Artan , Rees Catherine , Cassar Susan , Coventry Kris , Collignon Peter , Allerberger Franz , Rahube Teddie O. , Oliveira Guilherme , Ivanov Ivan , Vuthy Yith , Sopheak Thet , Yost Christopher K. , Ke Changwen , Zheng Huanying , Baisheng Li , Jiao Xiaoyang , Donado-Godoy Pilar , Coulibaly Kalpy Julien , Jergović Matijana , Hrenovic Jasna , Karpíšková Renáta , Villacis Jose Eduardo , Legesse Mengistu , Eguale Tadesse , Heikinheimo Annamari , Malania Lile , Nitsche Andreas , Brinkmann Annika , Saba Courage Kosi Setsoafia , Kocsis Bela , Solymosi Norbert , Thorsteinsdottir Thorunn R. , Hatha Abdulla Mohamed , Alebouyeh Masoud , Morris Dearbhaile , Cormican Martin , O’Connor Louise , Moran-Gilad Jacob , Alba Patricia , Battisti Antonio , Shakenova Zeinegul , Kiiyukia Ciira , Ng’eno Eric , Raka Lul , Avsejenko Jeļena , Bērziņš Aivars , Bartkevics Vadims , Penny Christian , Rajandas Heraa , Parimannan Sivachandran , Haber Malcolm Vella , Pal Pushkar , Jeunen Gert-Jan , Gemmell Neil , Fashae Kayode , Holmstad Rune , Hasan Rumina , Shakoor Sadia , Rojas Maria Luz Zamudio , Wasyl Dariusz , Bosevska Golubinka , Kochubovski Mihail , Radu Cojocaru , Gassama Amy , Radosavljevic Vladimir , Wuertz Stefan , Zuniga-Montanez Rogelio , Tay Moon Y. F. , Gavačová Dagmar , Pastuchova Katarina , Truska Peter , Trkov Marija , Esterhuyse Kerneels , Keddy Karen , Cerdà-Cuéllar Marta , Pathirage Sujatha , Norrgren Leif , Örn Stefan , Larsson D. G. Joakim , Heijden Tanja Van der , Kumburu Happiness Houka , Sanneh Bakary , Bidjada Pawou , Njanpop-Lafourcade Berthe-Marie , Nikiema-Pessinaba Somtinda Christelle , Levent Belkis , Meschke John Scott , Beck Nicola Koren , Van Chinh Dang , Phuc Nguyen Do , Tran Doan Minh Nguyen , Kwenda Geoffrey , Tabo Djim-adjim , Wester Astrid Louise , Cuadros-Orellana Sara , Amid Clara , Cochrane Guy , Sicheritz-Ponten Thomas , Schmitt Heike , Alvarez Jorge Raul Matheu , Aidara-Kane Awa , Pamp Sünje J. , Lund Ole , Hald Tine , Woolhouse Mark , Koopmans Marion P. , Vigre Håkan , Petersen Thomas Nordahl , Aarestrup Frank M. 
Published: March 2019

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.