Antibiotic tolerance and resistance in clinical Escherichia coli isolates responsible of urinary tract infections
Internship title: Antibiotic tolerance and resistance in clinical Escherichia coli isolates responsible of urinary tract infections
Name: IAME, UMR 1137
Affiliation: UFR de Médecine de l’Université de Paris
Address: Site Bichat, 16 rue Henri Huchard, 75018 Paris
Name: Erick Denamur
Phone number: 0157277739
Name: Imane El Meouche – Olivier Tenaillon
Phone number: 0157277745
Subject Keywords: E. coli, antibiotic resistance, antibiotic tolerance, single-cell, evolution
Tools and methodologies: bacteriology, Molecular biology, fluorescence microscopy
Summary of lab’s interests: For more details: https://www.iame-research.center/
QEM directed by Olivier Tenaillon: unravels the dynamics of adaptation by combining theoretical and mechanistic models applied to quasi-exhaustive libraries of mutants at the gene or operon level, experimental evolution in vitro and in vivo, as well as inferences from phylogenetic and epidemiological data.
EVRest directed by Erick Denamur: achieves a better understanding of the ecological, evolutionary and molecular parameters allowing the adaptation of natural isolates of the Escherichia coli species to their various lifestyles, especially those involved in the emergence of virulence and antimicrobial resistance and develops new original therapeutic approaches to fight this pathogen.
Project summary: The project will focus on pathogenic extraintestinal Escherichia coli strains starting by determining their resistance and tolerance profiles to antibiotic exposure in various media such as LB, M9, urine etc. Then, strains with different levels of tolerance where bacteria can survive antibiotic treatments without having acquired a resistance genotype will be selected. Single-cell studies will then be performed on selected genes to study their importance in antibiotic resistance at the single cell level.
Studying antibiotic resistance in pathogenic isolates and in relevant media will mirror behaviors in conditions closer to medical contexts. As bacterial fitness is different from an environment to the other, this project will give us the opportunity to find novel genes in surviving and tolerating antibiotic treatment in more realistic environments. It will also extend our knowledge to explore their heterogeneity within clonal populations, their role in bet-hedging, and further in the emergence of mutations and resistance.
Interdisciplinary aspect of the project: This project will combine phenotypic and molecular approaches, microscopy and evolutionary modules. It is a great alliance between basic and clinical research. The lab is experienced in both theoretical and experimental adaptation and evolution of E. coli.
Single-cell techniques and population-based evolutionary studies will be adapted to understand better the emergence of antibiotic resistance in clinically relevant strains and environments.