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Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements - identification of sources by whole genome sequencing

English title Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements - identification of sources by whole genome sequencing
Applicant Tschudin-Sutter Sarah
Number 167060
Funding scheme NRP 72 Antimicrobial Resistance
Research institution Klinik für Infektiologie und Spitalhygiene Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Internal Medicine
Start/End 01.05.2017 - 31.08.2020
Approved amount 601'763.00
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Keywords (5)

Mobile genetic elements; Transmission; Whole genome sequencing; One health; ESBL-producing Enterobacteriaceae

Lay Summary (German)

Lead
Wir untersuchen anhand von Proben aus der Stadt Basel, welche Rolle unterschiedliche Quellen wie Spitäler, Nahrungsmittel und Abwasser bei der Verbreitung von antibiotikaresistenten Bakterien spielen.
Lay summary

Zu den häufigsten bakteriellen Krankheitserregern beim Menschen gehören einige Gattungen der Enterobakterien. Viele davon sind mittlerweile resistent gegen Antibiotika. Sie finden sich in Spitälern, aber ebenso auf Nahrungsmitteln oder im Abwasser. Wir untersuchen, welchen Beitrag diese einzelnen Quellen zur Verbreitung resistenter Enterobakterien leisten. Dazu analysieren wir mehrere hundert Bakterienstämme, die bei Patienten im Universitätsspital Basel, auf Lebensmitteln aus dem Detailhandel und im Abwasser der Stadt Basel gefunden wurden. Mit molekulargenetischen Methoden bestimmen wir, welche Bakterien genetisch verwandt sind. So lassen sich die Verbreitungswege einzelner Bakterienstämme nachvollziehen und es wird deutlich, welche Rolle die verschiedenen Quellen dabei spielen.

Hintergrund
Lange glaubte man, dass für die schnelle Verbreitung von antibiotikaresistenten Bakterien hauptsächlich die Übertragung in Spitälern verantwortlich sei. Doch in jüngerer Zeit wurden resistente Keime auch auf Nahrungsmitteln und in Abwässern nachgewiesen. Diese Quellen dürften ebenfalls eine wichtige Rolle spielen.

Ziel
Wir wollen die Übertragungsketten einzelner antibiotikaresistenter Bakterienstämme in der Stadt Basel aufdecken, unter Berücksichtigung von Quellen innerhalb und ausserhalb von Spitälern.

Bedeutung
Die genaue Kenntnis über Quellen und Übertragungswege ist im Kampf gegen antibiotikaresistente Bakterien zentral. Sie ermöglicht es, Präventionsmassnahmen an den entscheidenden Punkten zu ergreifen.

Direct link to Lay Summary Last update: 08.12.2017

Lay Summary (French)

Lead
Au moyen d’échantillons prélevés dans la ville de Bâle, nous étudions quels rôles les différentes sources que constituent les hôpitaux, les produits alimentaires et les effluents jouent dans la propagation de bactéries résistantes aux antibiotiques.
Lay summary

Certaines entérobactéries comptent parmi les agents pathogènes les plus fréquemment rencontrés. Nombre d’entre elles sont devenues résistantes aux antibiotiques et se retrouvent dans les hôpitaux, les aliments et les effluents. Nous étudions dans quelle mesure ces différentes sources contribuent à la propagation des germes. A cette fin, nous analysons plusieurs centaines de souches bactériennes prélevées sur des patients de l’hôpital universitaire de Bâle, sur des produits alimentaires du commerce de détail et dans les effluents de la ville. Grâce à la génétique moléculaire, nous déterminons quelles bactéries sont génétiquement apparentées, afin d’identifier les voies de propagation des souches étudiées et de comprendre le rôle joué par les différentes sources dont elles sont issues.

Contexte
On a longtemps pensé que la transmission via les hôpitaux était la principale explication à la propagation rapide des bactéries résistantes aux antibiotiques. Il a néanmoins récemment été démontré que des germes résistants étaient également présents sur les produits alimentaires et dans les effluents. Il est donc probable que ces sources jouent aussi un rôle important dans le phénomène de propagation.

Objectif
Nous souhaitons identifier les chaînes de propagation de différentes souches de bactéries résistantes aux antibiotiques dans la ville de Bâle en prenant en compte des sources internes et externes aux hôpitaux.

Importance
La connaissance exacte des sources et des voies de propagation revêt une importance primordiale pour la lutte contre les bactéries résistantes aux antibiotiques. Les informations recueillies permettront d’adopter les mesures de prévention adéquates aux points stratégiques.


Direct link to Lay Summary Last update: 08.12.2017

Lay Summary (English)

Lead
We are using samples obtained from the Basel urban region to investigate the role played by different sources such as hospitals, foodstuffs and waste water in the spread of antibiotic-resistant bacteria.
Lay summary

The most common bacterial pathogens in humans include several species of the family of Enterobacteriaceae. Many of them have now become resistant to antibiotics. They occur in hospitals and also on food and in waste water. We are studying the contribution made by each of these sources to the spread of resistant Enterobacteriaceae. To do this we are analysing several hundred bacterial strains found in patients at University Hospital Basel, on food obtained from retail outlets and in waste water from the city of Basel. We are using molecular genetic methods to determine which bacteria are genetically related. By doing so we can identify the ways in which individual bacterial strains spread and highlight the role played by the different sources.

Background
For a long time it was thought that transmission in hospital was the main factor in the rapid spread of antibiotic-resistant bacteria. More recently, though, resistant germs have also been found on food and in waste water. These sources are also likely to play an important role.

Aim
Our aim is to identify the transmission chains of individual antibiotic-resistant bacterial strains in the Basel urban region, taking into account sources both within and outside hospitals.

Relevance
Precise information about sources and transmission routes is of central importance in the fight against antibiotic-resistant bacteria. It enables preventive measures to be deployed in crucial locations.


Direct link to Lay Summary Last update: 08.12.2017

Responsible applicant and co-applicants

Employees

Publications

Publication
Identification of a cluster of Extended-Spectrum Beta-Lactamase producing Klebsiella pneumoniae sequence type 101 isolated from food and humans
Aguilar-Bultet Lisandra, Bagutti Claudia, Egli Adrian, Alt Monica, Maurer Pekerman Laura, Schindler Ruth, Furger Reto, Eichenberger Lucas, Roloff Tim, Steffen Ingrid, Huebner Philipp, Stadler Tanja, Tschudin-Sutter Sarah (2020), Identification of a cluster of Extended-Spectrum Beta-Lactamase producing Klebsiella pneumoniae sequence type 101 isolated from food and humans, in Clinical Infectious Diseases, Online ahe.
Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements-identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland.
Stadler Tanja, Meinel Dominik, Aguilar-Bultet Lisandra, Huisman Jana, Schindler Ruth, Egli Adrian, Seth-Smith Helena, Eichenberger Lucas, Brodmann Peter, Hübner Philipp, Bagutti Claudia, Tschudin-Sutter Sarah (2018), Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements-identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland., in BMJ Open, e021823.

Collaboration

Group / person Country
Types of collaboration
Prof. S. Bonhoeffer/Institut für integrative Biologie, ETH Zürich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Annual congress of the Swiss Society for Microbiology 2018, 28.-30.8.18, Lausanne, Switzerland Talk given at a conference Assessing phylogenetic relatedness and plasmid transmission in ESBL-producing Enterobacteriaceae. 28.08.2018 Lausanne, Switzerland Stadler Tanja; Tschudin-Sutter Sarah; Aguilar Bultet Lisandra;
Annual congress of the Swiss Society for Microbiology 2018, 28.-30.8.18, Lausanne, Switzerland: Talk given at a conference Phylogenetics of bacteria and their plasmids: comparing bioinformatic approaches 28.08.2018 Lausanne, Switzerland Stadler Tanja; Tschudin-Sutter Sarah; Aguilar Bultet Lisandra;
NRP72 Meeting April 18th 2018, Nottwil, Switzerland Poster Phylogenetics of bacteria and their plasmids: comparing bioinformatic approaches 18.04.2018 Nottwil, Switzerland Stadler Tanja; Tschudin-Sutter Sarah; Aguilar Bultet Lisandra;
NRP72 Meeting April 18th 2018, Nottwil, Switzerland Poster Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements – identification of sources by whole genome sequencing 18.04.2018 Nottwil, Switzerland Aguilar Bultet Lisandra; Stadler Tanja; Tschudin-Sutter Sarah;
NRP72 Meeting April 18th 2018, Nottwil, Switzerland Poster Assessing phylogenetic relatedness and plasmid transmission in ESBL-producing Escherichia coli. 18.04.2018 Nottwil, Switzerland Aguilar Bultet Lisandra; Stadler Tanja; Tschudin-Sutter Sarah;


Abstract

Over the last decade, the world has witnessed a dramatic rise of multidrug-resistant gram-negative bacteria. This trend is reflected by a significant increase of resistance to third-generation cephalosporins in Klebsiella pneumoniae and Escherichia coli over the last years at EU level, the most important underlying resistance mechanism being the production of extended-spectrum beta-lactamases (ESBLs). In Switzerland, third-generation cephalosporin resistance in K. pneumonia and E. coli increased concomitantly from less than 2% in 2004 to 11% in 2013. ESBL-producing Enterobacteriaceae were first described in relation with hospital-acquired infections. In the 2000s, the epidemiology of ESBL-producing organisms changed as especially ESBL-E. coli was increasingly described as an important cause of community-acquired urinary tract infections worldwide, supporting the hypothesis that in more recent years ESBL-producing Enterobacteriaceae have probably been imported into hospitals rather than vice versa. Possible community-sources may include foodstuffs and colonization resulting from global travel. Transmission of ESBL-producing Enterobacteriaceae is complicated by ESBL genes being encoded on self-transmissible plasmids, which can be exchanged among the same and different species of Enterobacteriaceae. The respective contribution of horizontal gene transfer and exchange of plasmids carrying ESBL genes between Enterobacteriaceae to the rapidly expanding epidemiology of ESBL-producers, however, remains elusive.In contrast to conventional typing techniques, such as pulsed-field gel electrophoresis or multilocus sequence typing, whole genome sequencing allows the identification of single-nucleotide polymorphisms that differentiate bacterial strains and mobile genetic elements, such as plasmids at the highest possible resolution, therefore enabling investigation of their relatedness by phylogenetic analyses and ultimately detailed exploration of transmission pathways. This technique has currently been established at our microbiology laboratory and has to date not been applied to determine transmission of both strains and plasmids in a large epidemiological study including clinically relevant ESBL-Enterobacteriaceae-strains, as well as strains recovered from community settings. At our institution, all ESBL-producing Enterobacteriaceae recovered from any specimens obtained by routine clinical practice in both in and outpatient settings have been collected and stored since 2003, representing a unique collection of clinically relevant strains over time.The aim of this research project is to quantity the specific proportion of hospital-wide transmission of ESBL-producing Enterobacteriaceae on both the level of bacterial species and the mobile genetic elements, and to determine if hospital-acquired infections caused by ESBL-producers are related to strains and mobile genetic elements predominantly circulating in the community or in the healthcare setting. This distinction is critical in prevention since the former emphasizes the urgent need to establish or reinforce antibiotic stewardship programs, and the latter would call for more rigorous infection control. The specific aims of this research project include:i) To quantify the extent of hospital-wide transmission of ESBL-producing Enterobacteriaceae by assessing the genetic relatedness of ESBL-producing Enterobacteriaceae among patients and over time.ii) To estimate the contribution of horizontal gene transfer to the spread of ESBL-producing Enterobacteriaceae in both hospital-and community settingsiii) To determine migration of ESBL-producing Enterobacteriaceae between humans and their environment (i.e. foodstuff and wastewater samples) by comparing genetic relatedness of strains recovered from patients and the environment, in the sense of a “one-health”-approach.
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