ResistEpist | Dissection of the mechanisms causing the epistasis between antibiotic resistance mutations in Escherichia coli

Summary
Antibiotic resistance is a major threat to public health. Bacteria can become resistant by acquiring genes that counteract the action of antibiotics or by mutation of their targets. These targets are usually involved in essential processes and typically resistance mutations can impair bacterial growth in absence of antibiotics. However, combination of certain mutated alleles can result in an alleviation of this cost, thus favouring the acquisition of multiple resistances. This project aims to understand the mechanisms underlying the epistasis between resistance mutations. Decreased biosynthesis has been considered the main cause of the fitness cost associated to antibiotic resistance mutations. However, our preliminary results suggest the existence of additional causes, such as genomic instability or proteostasis imbalance. The study of these phenotypes in single and double resistant mutants of Escherichia coli will allow us to determine the nature of these epistatic interactions, as well as further understanding essential biological processes, and will provide information for the development of new treatments against multi-resistant infections.
Unfold all
/
Fold all
More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/746690
Start date: 01-12-2018
End date: 01-02-2021
Total budget - Public funding: 148 635,60 Euro - 148 635,00 Euro
Cordis data

Original description

Antibiotic resistance is a major threat to public health. Bacteria can become resistant by acquiring genes that counteract the action of antibiotics or by mutation of their targets. These targets are usually involved in essential processes and typically resistance mutations can impair bacterial growth in absence of antibiotics. However, combination of certain mutated alleles can result in an alleviation of this cost, thus favouring the acquisition of multiple resistances. This project aims to understand the mechanisms underlying the epistasis between resistance mutations. Decreased biosynthesis has been considered the main cause of the fitness cost associated to antibiotic resistance mutations. However, our preliminary results suggest the existence of additional causes, such as genomic instability or proteostasis imbalance. The study of these phenotypes in single and double resistant mutants of Escherichia coli will allow us to determine the nature of these epistatic interactions, as well as further understanding essential biological processes, and will provide information for the development of new treatments against multi-resistant infections.

Status

CLOSED

Call topic

MSCA-IF-2016

Update Date

28-04-2024
Images
No images available.
Geographical location(s)
Structured mapping
Unfold all
/
Fold all
Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2016
MSCA-IF-2016