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AMR and Plasmids: One Health undercover transmission

Projectomschrijving

Antibioticaresistentie van bacteriën is een groot probleem, omdat behandeling van bacteriële infecties met antibiotica dan onmogelijk wordt. Uit eerder onderzoek is gebleken dat de toename van resistente bacteriën niet komt door verspreiding van deze bacteriën van dier naar mens. Het kan zijn dat niet de bacteriën zelf, maar alleen de stukjes DNA uit die bacteriën worden overgedragen die zorgen voor het resistent worden.


In dit project wordt onderzocht hoe antibioticaresistentie op DNA niveau zich kan verspreiden tussen bacteriën. In het eerdere “i-4-1-Health” project zijn 450 resistente bacteriën verzameld bij mensen en dieren. Deze bacteriën zullen met nieuwe DNA analyse technieken worden ontleed. Dan wordt duidelijk welke DNA stukken die resistentie veroorzaken zich verspreiden.


Dit onderzoek zal laten zien hoe antibioticaresistentie zich verspreid tussen verschillende bacteriën en tussen mens en dier. Daarna kunnen manieren worden ontwikkeld om deze verspreiding te voorkomen.

Verslagen


Samenvatting van de aanvraag

Extended-spectrum beta-lactamase- and carbapenemase-producing Enterobacteriaceae (ESBL-E and CPE) contribute considerably to the disease burden of hospitalised patients (1). Gut carriage in humans of ESBL-E has increased over the years from <2% in 2010 to 10% in 2019 (2). A One-Health approach to study the dynamics of phenotypic and genotypic spread of resistance and transmission of AMR resistant bacteria is needed to elucidate whether spread between and within domains (livestock and humans) and possible reservoirs of resistance genes play a role in the increased prevalence of ESBL-E and future risks of transmission. In the recent EU funded i-4-1-health project, perianal or faecal swabs were collected from livestock, children in daycare and patients in healthcare facilities (hospital and long-term care facilities) in the Netherlands Belgian cross-border region. Phenotypic resistance characterisation and whole genome sequencing with NGS on the MiSeq platform was performed on the isolated ESBL-E and CPE bacteria to confirm the presence of AMR genes and to assess clonal relatedness of the bacterial isolates. For the Netherlands, this demonstrated an overall ESBL-E prevalence in humans of approximately 7%, while only sporadic events of clonal transmission were observed (manuscript in preparation). Unfortunately, the contribution of horizontal transfer of resistance-encoding plasmids and mobile genetic elements which facilitate the spread of AMR genes could not be studied, as complete reconstruction of plasmids and other mobile genetic elements from short-read NGS data is not feasible. About 450 ESBL-E and CPE isolates from different domains were collected at 3 sampling periods within a one-year time frame, providing an ideal dataset to analyse genotypic resistance within a limited time frame. In this project we will use this dataset to analyse the 450 ESBL-E and CPE isolates with long read sequencing on the MinIon nanopore platform, to assess the contribution of plasmids and/or mobile genetic elements in transmission of resistance in non-clonally related isolates. This might distinguish which resistance genes have a high risk of spread between and within domains, giving the possibility of prediction of potential spread. Specific screening for high risk genes might help in cost-effective infection prevention. Overall, further knowledge on the mechanisms of the spread of AMR genes will have a public health impact, as this can guide and optimise the implementation of control and preventive measures.

Onderwerpen

Kenmerken

Projectnummer:
541003006
Looptijd: 100%
Looptijd: 100 %
2020
2023
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. L.B. van Alphen
Verantwoordelijke organisatie:
Maastricht University