The impact of Host restriction of Escherichia coli on Transmission dynamics and spread of antimicrobial Resistance
The prevalence of antimicrobial resistance (AMR) is increasing rapidly worldwide, including in bacteria colonizing healthy human and animal populations. The recent reports of plasmid mediated colistin resistance, potentially associated with colistin usage in agriculture, further raise fears of infections that have become untreatable due to AMR. The commensal flora of humans and animals is a reservoir of AMR encoding genes and Escherichia coli in particular can carry multiple AMR determinants. Antimicrobial resistance transmission within E. coli appears dominated by certain lineages. To what extent these are restricted to certain host species is unknown. Such host restriction may be an important determinant of the likelihood of transmission of resistant E. coli between different reservoirs, such as between animal and human hosts. The identification of determinants that allow disentanglement of the different modes of resistance transmission (i.e. bacteria vs mobile genetic elements such as plasmids) is crucial for a more targeted design of interventions to prevent and reduce transmission of resistance. The proposed research aims to identify determinants of host restriction of E. coli and their potential association with antimicrobial resistance transmission and prevalence. We propose a One Health approach using mixed methods, including whole genome sequencing of a large collection of E. coli isolates from human, animal and environmental sources in different geographic areas across Europe and in Vietnam, experimental models to study the role of host restriction determinants in transmission and bacterial fitness, and mathematical modelling.
- Constance Schultsz, University of Amsterdam, Netherlands (Coordinator)
- Christian Menge, Friedrich-Loeffler-Institut, Germany (Partner)
- Torsten Semmler, Robert Koch Institute, Germany (Partner)
- Roberto Marcello La Regione, University of Surrey, United Kingdom (Partner)
- Lucas Domínguez Rodríguez, VISAVET Health Surveillance Centre, Spain (Partner)
- Stefan Schwarz, Freie Universität Berlin, Germany (Partner)
- Hoa Ngo Thi, University of Oxford, United Kingdom (Partner)
Bacteria are increasingly resistant to antibiotics, threatening treatment of bacterial infections. Antibiotic resistance (ABR) is encoded in the DNA of the bacteria. ABR is spreading rapidly in human and animal populations because resistant bacteria are transmitted or because bacteria can transfer DNA encoding ABR to other bacteria which then also become resistant. Escherichia coli resistant to specific antibiotics are considered a high priority risk. Transfer of such E. coli between animals, such as livestock, and humans may contribute to the spread of ABR. The HECTOR project set out to understand if certain E. coli are adapted to certain host species (human or animal) and how this adaptation is encoded by the DNA. Through genome comparison of 1198 E. coli strains, we found which E. coli strains are associated with human host, and which parts of their DNA aid in this adaptation. We discovered that the DNA encodes metabolic activities allowing E. coli to potentially survive better in the human gut. In addition, we studied survival and ABR transfer of E. coli adapted to different host species, in live pigs and calves, and in laboratory experiments imitating the chicken gut. We identified E. coli strains which are better able to survive in these models than other strains. However, our findings highlight the complexity of host adaptation, as we could not identify E. coli types surviving and growing well in either model. Furthermore, we observed that transfer of DNA encoding ABR is rare in such experimental conditions. The research of HECTOR has advanced our understanding of why some bacteria are able to spread between animal and human populations, thus contributing to the spread of ABR, and why others cannot. This can be helpful for risk assessment.
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