Wastewater Based Epidemiology Enabled Surveillance of Antibiotic Resistance

Abstract

Wastewater-based epidemiology (WBE) for disease monitoring is highly promising, but requires consistent methodologies that incorporate predetermined objectives, targets, and metrics. We demonstrate a comprehensive metagenomics-based approach for global surveillance of antibiotic resistance in sewage, enabling assessment of: 1) which antibiotic resistance genes (ARGs) are shared across regions/communities; 2) which ARGs are discriminatory; and 3) factors associated with overall trends including antibiotic concentrations in sewage. Across an internationally-sourced transect of sewage samples collected using a centralized, standardized protocol, ARG relative abundances (16S rRNA gene-normalized) were highest in Hong Kong and India and lowest in Sweden and Switzerland, reflecting national policy, measured antibiotic concentrations, and metal resistance genes. Asian versus European/US resistomes were distinct, with macrolide-lincosamide-streptogramin, phenicol, quinolone, and tetracycline versus multidrug resistance ARGs being discriminatory, respectively. Sales data were not predictive of antibiotics measured in sewage, emphasizing need for direct measurements. The WBE approach defined herein demonstrates multi-site comparability and sensitivity to local/regional factors.

Wastewater surveillance of antibiotic-resistant bacterial pathogens: A systematic review

“…Except for one study, studies conducted at the international level used shotgun metagenomics or high-throughput PCR and reported the geographic “hot spots” of ARB ( Hendriksen et al, 2019b ; Pärnänen et al, 2019 ; Riquelme et al, 2021 ). These studies reported a relative abundance of ARB, and resistance genes.…”

“…Other studies have used shotgun metagenomics for WWS of ARB. This approach was mostly used for surveillance over a large geographical area ( Forslund et al, 2013 ; Petersen et al, 2015 ; Hendriksen et al, 2019b ; Riquelme et al, 2021 ). It yields the bacterial diversity and abundance, and an inventory of all ARGs as a comprehensive overview of the environmental resistome, an abundance of ARG reads that confers resistance to antibiotic classes ( Manageiro et al, 2014 ; Hendriksen et al, 2019c ).…”

Wastewater-Based Epidemiology for monitoring community derived antimicrobials and resistance genes: a one-year longitudinal study

“…The development of advanced DNA sequencing techniques offers a promising approach for monitoring the abundance of ARGs in the environment (Guo et al, 2017;Hendriksen et al, 2019;Lanza et al, 2018;Petrovich et al, 2020;Riquelme et al, 2021). High throughput quantitative polymerase chain reaction (qPCR) has also been utilised to reflect expected clinical resistance trends across Europe (Pärnänen et al, 2019).…”

“…antimicrobials, genes, co-factors) to be studied simultaneously to give a full picture of AMR prevalence at a community level. (Elder et al, 2021) 25 AAs --Athens, Greece 7 days, prepandemic 15 days in 2020 (Galani et al, 2021) 45 AAs Anhydro erythromycin Acetylsulfamethoxazole Metagenomic untargeted shotgun sequencing 12 WWTPs, 6 countries 14 influent samples each site (Riquelme et al, 2021;Singh et al, 2019) Due to the multifaceted nature of AMR, the One Health approach has proved a valuable framework for tackling this complex issue. One Health aims at holistic understanding and management of public and environmental health, and has been successfully adopted in AMR research with considerable global human and animal health, food security, and safety impacts.…”

Sensitivity and consistency of long- and short-read metagenomics and epicPCR for the detection of antibiotic resistance genes and their bacterial hosts in wastewater

“…One of the most widely used methods to analyze antibiotic resistance in wastewater is metagenomic sequencing [31][32][33] . Next-generation sequencing (i.e., short-read) coupled with de novo assembly recovers ARG-host and ARG-MGE linkages by screening taxonomical markers and MGEs on the assembled ARG-carrying contigs 29,34,35 .…”