Project description
Competing for the same niche: a new strategy against antibiotic resistance
Many bacteria such as Escherichia coli evolve mechanisms to fight the effect of antibiotics. An example of such a strategy is the expression of extended-spectrum beta-lactamases (ESBLs), enzymes that break down penicillin and cephalosporins, rendering them ineffective against infections. To contribute to the development of new treatments, the EU-funded ECOSTRAT project proposes to study the evolution of ESBL-producing E. coli. Researchers will investigate the colonisation of the mammalian gut by ESBL E. coli to identify determinant factors and genes. Results will lay the foundation for novel treatments that rely on the competition with other microbiota.
Objective
The rise of multidrug-resistant bacteria limits the options to treat critically ill patients. In 2015, Escherichia coli producing Extended Spectrum β-Lactamases (ESBL) were the leading cause of death attributable to antibiotic resistant bacteria in Europe. The failure to address these infections using standard antibiotherapy calls for better understanding of how these bacteria evolve in order to develop new treatments.
Presence of resistance and virulence genes correlates with high prevalence in ESBL clones. Since the intestinal tract of mammals represents a major ecological niche for E. coli, gut colonization ability must have predisposed certain clones to evolutionary success during the antibiotic era. In particular, competition against the gut microbiota should select for colonization factors that predate the acquisition of resistance.
To test this hypothesis, we will compare strategies for gut colonization in ESBL clones of different prevalence in absence of antibiotics. Using mice, we will be able to modulate selective pressures exerted by the intestinal microbiota. We will compare gut colonization factors in ESBL clones by performing parallel high-throughput genetic screening in conventional mice (aim 1). We will analyze adaptability and the stability of resistance and virulence genes during long-term colonization (aim 2). Subsequent competitions in gnotobiotic mice harboring permissive microbiota will allow us to deduce functions needed for colonization in the presence of a competitive microbiota. In aim 3, we will measure the impact of competitors transmitted from cohabitant to infected mice on the duration of ESBL E. coli carriage and assess potential synergies with the adaptive immunity in vaccinated hosts.
Overall, we will unravel with unprecedented depth the general principles of intestinal colonization in ESBL E. coli, shed new light on the global success of prevalent clones and conceptualize robust antibiotic-free competition-based treatments.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences microbiology bacteriology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs antibiotics
- natural sciences biological sciences zoology mammalogy
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-COG - Consolidator Grant
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2020-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
4051 Basel
Switzerland
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