Association of the gut microbiota mobilome with hospital location and birth weight in preterm infants

Ray, Anuradha; Estensmo, Eva Lena; Abée-Lund, Trine M L’; Foley, Steven L.; Allgaier, Bernhard; Martin, Camilia R.; Claud, Erika C.; Rudi, Knut

doi:10.1038/pr.2017.146

Cited by 20 publications

(17 citation statements)

References 37 publications

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“…Although, there are several lines of bioinformatics evidence of extensive HGT in the human commensal gut microbiota, this has not yet been experimentally proven (3,4,(23)(24)(25). In the current work we have experimentally shown frequent transmission of MGE between gut associated bacteria, and laboratory strains.…”

Section: Discussionmentioning

confidence: 62%

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Experimental support for multidrug resistance transfer potential in the preterm infant gut microbiota

et al. 2019

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Background. There is currently a lack of experimental evidence for horizontal gene transfer (HGT) mechanisms in the human gut microbiota. The aim of this study was therefore to experimentally determine the HGT potential in the microbiota of a healthy preterm infant twin pair, and to evaluate the global occurrence of the mobilized elements. Methods. Stool samples were collected. Both shotgun metagenome sequencing and bacterial culturing were done for the same samples. A range of experimental conditions were used to test DNA-transfer for the cultured isolates. Searches for global distribution of transferable elements were done for the ~120,000 metagenomic samples in the SRA-database. Results. DNA transfer experiments demonstrated frequent transmission of an ESBL encoding IncI1 plasmid, a high copy number ColEI plasmid, and bacteriophage P1. Both IncI1 and ColE1 were abundant in the stool samples. In vitro competition experiments showed that transconjugants containing IncI1 plasmids outcompeted the recipient strain in the absence of antibiotic selection. The SRA-searches indicated a global distribution of the mobilizable elements, with chicken identified as a possible reservoir for the IncI1 ESBL encoding plasmid. Conclusion. Our results experimentally support a major horizontal transmission and persistence potential of the preterm infant gut microbiota mobilome involving genes encoding ESBL.

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Section: Discussionmentioning

confidence: 62%

“…Recent culture independent work has indicated high levels of horizontal gene transfer (HGT) in the human gut (3). This enables the potential for transmission of antibiotic resistance -(ARG) and virulence genes within the preterm infant gut microbiota (4).…”

Section: Introductionmentioning

confidence: 99%

Experimental support for multidrug resistance transfer potential in the preterm infant gut microbiota

et al. 2019

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“…ResFinder -Metagenomic read-mapping outperformed cultivation-based techniques in terms of predicting expected tetracycline resistance based on farm antimicrobial consumption Weinroth et al (2018) Bovine faecal samples during a clinical trial using ceftiofur and chlortetracycline MEGARes -Treatment with ceftiofur was not associated with changes in b-lactam resistance genes -Treatment with chlortetracycline had a significant increase in relative abundance of tetracycline resistance genes -There was an increase in resistance to an antimicrobial class not administered during the study, which is a possible indication of co-selection of resistance genes Munk et al (2018) Samples from pig and poultry farms ResFinder -Higher AMR gene loads were observed in pig farms, whereas poultry resistomes were more diverse -Several critical AMR genes, including mcr-1 and optrA, were detected, the abundance of which differed both between host species and between countries -The total acquired AMR genes level was associated with the overall country-specific antimicrobial usage in livestock The main advantages of shotgun metagenomics over classical methods for analysing the resistome is that this methodology is faster, allows for the simultaneous detection of a vast number of resistance genes of different microbial origins within a given sample and the estimation of their relative abundance, and in some cases it is possible to get important information on the genetic background of the detected AMR determinants (microbial species or strain of origin and/or association with mobile genetic elements, such as plasmids, integrons, transposons, prophages, etc.). In fact, shotgun metagenomics can be also used to characterise the so-called mobilome (pool of mobile genetic elements) in a given sample (Ravi et al, 2017). However, the attribution of the identified resistance genes to specific taxa or strains and their identification as transferable or non-transferable resistance determinants is not possible in most cases yet, which would hamper the assessment of the risk posed by such AMR determinants.…”

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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“…The reasons for these specific plasmid-host combinations remain elusive; however, we found that IncI and IncB/O plasmids displayed the highest in vitro conjugation efficiencies compared to other ESBL-encoding plasmids. Moreover, the IncB/O plasmid group was found to be the second most commonly identified plasmid group in commensal and pathogenic E. coli from humans and animals 75 , while the conjugative IncI group was can also be highly prevalent in commensal bacteria from infants 76 . The regular sampling of these plasmids by cipR S. sonnei could be attributed to several factors, including the close genetic relatedness between Shigella and E. coli , the propensity of S. sonnei to acquire AMR plasmids, and the circulation of highly transmissible AMR plasmids in commensal E. coli .…”

Section: Discussionmentioning

confidence: 99%

Ciprofloxacin facilitates the transfer of XDR plasmids from commensalE. coliinto epidemic fluoroquinolone-resistantShigella sonnei

Pham

Nguyen

Duong

et al. 2019

Preprint

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The global dissemination of a ciprofloxacin-resistant (cipR) S. sonnei clone outlines the mobility of this important agent of diarrheal disease, and threatens the utility of ciprofloxacin as a first-line antimicrobial for shigellosis. Here, we aimed to track the emergence of cipR S. sonnei in Vietnam to understand how novel antimicrobial resistant (AMR) Shigella clones become established in new locations. From 2014 to 2016, we isolated and genome sequenced 79 S. sonnei from children hospitalized with dysenteric diarrhea in southern Vietnam. The novel cipR S. sonnei clone displaced the resident ciprofloxacin-susceptible lineage while acquiring resistance against third-generation cephalosporins, macrolides, and aminoglycosides. This process was not the result of a single clonal expansion, as we identified at least thirteen independent acquisitions of ESBL-encoding plasmids. The frequency and diversity of the variable AMR repertoire in an expanding clonal background of S. sonnei is unprecedented and we speculated that it was facilitated by horizontal gene transfer from commensal organisms in the human gut. Consequently, we characterized non-Shigella Enterobacteriaceae from Shigella-infected and healthy children by shotgun metagenomics. We identified a wide array of AMR genes and plasmids in the commensal Enterobacteriaceae, including an E. coli isolated from a Shigella-infected child with an identical ESBL plasmid to that characterized in the infecting S. sonnei. We confirmed that these AMR plasmids could be exchanged between commensal E. coli and S. sonnei and found that supplementation of ciprofloxacin into the conjugation media significantly increased the conjugation frequency of IncI/blaCTX-M-15, IncB/O/blaCTX-M-27 and IncF/blaCTX-M-27 plasmids. In a setting with high antimicrobial use and a high prevalence of AMR commensals, cipR S. sonnei may be propelled towards pan-resistance by adherence to outdated international treatment guidelines. Our work highlights the role of the gut microbiota in transferring resistance plasmids into enteric pathogens and provides essential data to restrict the use of ciprofloxacin globally.

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Association of the gut microbiota mobilome with hospital location and birth weight in preterm infants

Cited by 20 publications

References 37 publications

Experimental support for multidrug resistance transfer potential in the preterm infant gut microbiota

Experimental support for multidrug resistance transfer potential in the preterm infant gut microbiota

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

Ciprofloxacin facilitates the transfer of XDR plasmids from commensalE. coliinto epidemic fluoroquinolone-resistantShigella sonnei

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