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

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

doi:10.1038/s41467-019-08853-3

Cited by 780 publications

(638 citation statements)

References 46 publications

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“…A theoretical solution to the spread of AMR could be to use different drug classes in animals on the assumption that distinct antimicrobial selection pressures would sustain efficacy of drugs in humans. However, even if this was feasible, evidence from this study (and others (Hendriksen et al ., )) shows that multidrug resistant bacteria can be isolated and cultured from sewage, presenting a potential route for transmission of AMR in the environment. While the sources and implications of environmental contamination remain controversial (Rizzo et al ., ; Munck et al ., ), the evidence in our study is consistent with the horizontal transfer of AMR among Campylobacter isolated from livestock, humans and sewage.…”

Section: Discussionmentioning

confidence: 99%

Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease

Mourkas

Florez‐Cuadrado

Pascoe

et al. 2019

Environmental Microbiology

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Summary The use of antimicrobials in human and veterinary medicine has coincided with a rise in antimicrobial resistance (AMR) in the food‐borne pathogens Campylobacter jejuni and Campylobacter coli. Faecal contamination from the main reservoir hosts (livestock, especially poultry) is the principal route of human infection but little is known about the spread of AMR among source and sink populations. In particular, questions remain about how Campylobacter resistomes interact between species and hosts, and the potential role of sewage as a conduit for the spread of AMR. Here, we investigate the genomic variation associated with AMR in 168 C. jejuni and 92 C. coli strains isolated from humans, livestock and urban effluents in Spain. AMR was tested in vitro and isolate genomes were sequenced and screened for putative AMR genes and alleles. Genes associated with resistance to multiple drug classes were observed in both species and were commonly present in multidrug‐resistant genomic islands (GIs), often located on plasmids or mobile elements. In many cases, these loci had alleles that were shared among C. jejuni and C. coli consistent with horizontal transfer. Our results suggest that specific antibiotic resistance genes have spread among Campylobacter isolated from humans, animals and the environment.

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Section: Discussionmentioning

confidence: 99%

Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease

Mourkas

Florez‐Cuadrado

Pascoe

et al. 2019

Environmental Microbiology

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Section: Assessmentmentioning

confidence: 99%

“…In relation to hazard identification, as already mentioned under Section 3.5, metagenomics offers the possibility to produce in some cases consensus draft genomes of the strains of interest which would allow for a very rapid characterisation (virulence and AMR repertoire, among others) of the pathogenic strains present in a sample. For example, metagenomic sequencing of sewage has recently been suggested as a means of monitoring the occurrence of AMR genes in the general human population (Hendriksen et al, 2019b) and, in fact, AMR occurrence in wastewater treatment plants has been shown to mirror the clinical prevalence of phenotypic resistance in several bacterial species (P € arn € anen et al, 2019). Shotgun metagenomics provides information on the complete pool of microbial genes from a particular sample, and therefore can be used to infer the full repertoire of resistance determinants within such sample, although depending on the approach those determinants might not be assigned to particular taxa and it is still difficult to obtain information on the AMR determinants harboured by specific bacterial strains.…”

Section: Metagenomics In Food-borne Outbreak Detection/investigationmentioning

confidence: 99%

Whole genome sequencing and metagenomics for outbreak investigation, source attribution and risk assessment of food‐borne microorganisms

Koutsoumanis¹,

Allende²,

Álvarez‐Ordóñez³

et al. 2019

EFS2

104

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This Opinion considers the application of whole genome sequencing (WGS) and metagenomics for outbreak investigation, source attribution and risk assessment of food-borne pathogens. WGS offers the highest level of bacterial strain discrimination for food-borne outbreak investigation and sourceattribution as well as potential for more precise hazard identification, thereby facilitating more targeted risk assessment and risk management. WGS improves linking of sporadic cases associated with different food products and geographical regions to a point source outbreak and can facilitate epidemiological investigations, allowing also the use of previously sequenced genomes. Source attribution may be favoured by improved identification of transmission pathways, through the integration of spatial-temporal factors and the detection of multidirectional transmission and pathogenhost interactions. Metagenomics has potential, especially in relation to the detection and characterisation of non-culturable, difficult-to-culture or slow-growing microorganisms, for tracking of hazard-related genetic determinants and the dynamic evaluation of the composition and functionality of complex microbial communities. A SWOT analysis is provided on the use of WGS and metagenomics for Salmonella and Shigatoxin-producing Escherichia coli (STEC) serotyping and the identification of antimicrobial resistance determinants in bacteria. Close agreement between phenotypic and WGSbased genotyping data has been observed. WGS provides additional information on the nature and localisation of antimicrobial resistance determinants and on their dissemination potential by horizontal gene transfer, as well as on genes relating to virulence and biological fitness. Interoperable data will play a major role in the future use of WGS and metagenomic data. Capacity building based on harmonised, quality controlled operational systems within European laboratories and worldwide is essential for the investigation of cross-border outbreaks and for the development of international standardised risk assessments of food-borne microorganisms.

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“…Prescription levels for a particular antibiotic are unlikely to be of significant value in the surveillance of AMR in the regional community. Instead, determining the population resistome is significantly more informative 37 .…”

Section: Comparisons Between Oral and Gut Resistomes Reveal Differencmentioning

confidence: 99%

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

Carr

Witherden

Lee

et al. 2019

Preprint

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The global threat of the "antimicrobial resistance apocalypse" that has arisen in recent years has driven the use of high-throughput sequencing techniques to monitor the profile of resistance genes, known as the "resistome", in microbial populations. The human oral cavity contains a poorly explored reservoir of these genes, and little is known about their abundance and diversity, or how their profile compares with antimicrobial resistance genes in the gut. Here we analyse the resistome profiles of 788 oral cavities worldwide and compare these profiles with paired stool samples from shotgun metagenomic data. We find country and body site-specific differences in the prevalence of antimicrobial resistance genes, classes and mechanisms in oral and stool samples. However, the 1 1 abundance of these antimicrobial resistance classes do not correlate with antibiotic prescription rates. A greater similarity was found in interpersonal resistomes between the same body sites than intrapersonal resistomes across different body sites. Between individuals, the oral cavity contains the highest and lowest abundances of specific antimicrobial resistance genes, but a lower diversity of resistance genes compared to the gut, which is likely influenced by differences in microbial composition and exposure to antimicrobial selection pressures. Co-occurrence analysis shows contrasting ARG-species associations between saliva and stool samples. This is the first study to date that characterises the oral cavity resistome worldwide, identifying its distinctive signatures compared to the gut.Maintenance and persistence of antimicrobial resistance is likely to vary across different body sites. Thus, we highlight the importance of characterising the resistome across body sites to uncover the antimicrobial resistance potential in the human body.

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

Cited by 780 publications

References 46 publications

Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease

Gene pool transmission of multidrug resistance among Campylobacter from livestock, sewage and human disease

Whole genome sequencing and metagenomics for outbreak investigation, source attribution and risk assessment of food‐borne microorganisms

Abundance and diversity of resistomes differ between healthy human oral cavities and gut

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