HECTOR

The impact of host restriction of Escherichia coli on transmission dynamics and spread of antimicrobial resistance

Objective

The main objectives of the proposed research are:
1. To identify genomic determinants of host restriction to animal, human and environmental reservoirs
within E. coli populations on the basis of whole genome sequence analysis;
2. To assess potential associations between host restriction patterns and AMR prevalence focusing on
plasmid-encoded resistance of clinical relevance;
3. To experimentally establish the impact of host restriction determinants on exchange of resistant
bacteria and resistance genes between animals, humans and environment;
4. To model transmission dynamics of AMR E. coli between different hosts using mathematical
modeling; and
5. To characterize determinants that contribute to host restriction of E. coli in and between human,
animal and environmental reservoirs.


Description

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. The research should result in a risk-assessment, estimating the contribution of
different transmission routes and predicting the effect of interventions on a single route on the
overall prevalence in the different compartments. The consortium is uniquely placed to
perform this research as it consists of experts in the field of antimicrobial resistance, who work
in human and animal health domains, and represent highly complementary disciplines.


AIGHD Research Lead

Prof. dr. Constance Schultsz


Partners

Academisch Medisch Centrum

Friedrich-Loeffler-Institut

University of Surrey

Universidad Complutense de Madrid

The Chancellor, Masters and Scholars of the University of Oxford

Freie Universität Berlin

Universitair Medisch Centrum Utrecht

Stichting Amsterdam Institute for Global Health and Development


Funders

JPI-EC-AMR


Countries

Netherlands

UK

Spain

Germany