A5069101540- Antibiotic Resistance in Bacteria
- Evolution and Genetic Dynamics
- Escherichia coli research studies
- Evolutionary Game Theory and Cooperation
- Antibiotics Pharmacokinetics and Efficacy
- Gut microbiota and health
- Bacterial Genetics and Biotechnology
- CRISPR and Genetic Engineering
- Vibrio bacteria research studies
- Microbial Metabolic Engineering and Bioproduction
- Urinary Tract Infections Management
- Genomics and Phylogenetic Studies
- Plant Pathogenic Bacteria Studies
- Genetic diversity and population structure
- Gallbladder and Bile Duct Disorders
- Mathematical and Theoretical Epidemiology and Ecology Models
- Pharmaceutical and Antibiotic Environmental Impacts
- Bacterial biofilms and quorum sensing
Université Paris Cité
2016-2024
Inserm
2016-2024
Sorbonne Paris Cité
2016-2024
Université Sorbonne Paris Nord
2019-2024
Sorbonne Université
2021-2024
Institut Cochin
2022
Assistance Publique – Hôpitaux de Paris
2020-2021
Délégation Paris 7
2016-2020
Infection, Anti-microbiens, Modélisation, Evolution
2018
The distribution of fitness effects new mutations shapes evolution, but it is challenging to observe how changes as organisms adapt. Using
Ceftazidime-avibactam (CZA) and cefiderocol are recently commercialized molecules active against highly drug-resistant bacteria, including carbapenem-resistant members of the Enterobacteriaceae. Mutants resistant to CZA have been described, notably in Klebsiella pneumoniae carbapenemase (KPC) producers. Considering structural similarities between ceftazidime cefiderocol, we hypothesized that resistance KPC-producing Enterobacterales may lead cross-resistance cefiderocol.CZA-resistant mutants...
Although microbial ecology of the gut is now a major focus interest, little known about molecular determinants adaptation in gut. Experimental evolution coupled with whole-genome sequencing can provide insights adaptive process. In vitro experiments have revealed some conserved patterns: intermediate convergence, and epistatic interactions between beneficial mutations global regulators. To test relevance these patterns to identify selective pressures acting vivo, we performed long-term an E....
Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in more pronounced impact on the intestinal microbiota. We performed monocenter, randomized open-label clinical trial 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or g/8 for 3 days.
Despite a fitness cost imposed on bacterial hosts, large conjugative plasmids play key role in the diffusion of resistance determinants, such as CTX-M extended-spectrum β-lactamases. Among plasmids, IncF are most predominant group, and an F2:A1:B- IncF-type plasmid encoding CTX-M-15 variant was recently described being strongly associated with emerging worldwide Escherichia coli sequence type 131 (ST131)-O25b:H4 H30Rx/C2 sublineage. In this context, we investigated narrow-range F-type...
To explore the mutational possibilities of insertions and deletions (indels) in Klebsiella pneumoniae carbapenemase (KPC) beta-lactamase, we selected for ceftazidime-avibactam-resistant mutants. Of 96 screened mutants, obtained 19 indels (2 to 15 amino acids), all located loops surrounding active site. Three antibiotic susceptibility phenotypes emerged: an extended-spectrum-beta-lactamase-like phenotype, activity restricted ceftazidime, a carbapenem-susceptible KPC-like phenotype.
Our ability to predict the impact of mutations on traits relevant for disease and evolution remains severely limited by dependence their effects genetic background environment. Even when molecular interactions between genes are known, it is unclear how these translate organism-level alleles. We therefore characterized interplay environmental dependencies in determining fitness quantifying ~4000 expression variants two metabolic genes, starting from various environmentally modulated levels....
The recent emergence and diffusion in the community of Escherichia coli isolates belonging to multidrug-resistant CTX-M-27-producing sequence type 131 (ST131) C1-M27 cluster makes this potentially as epidemic worldwide E. ST131 subclade C2 composed producing CTX-M-15. Thirty-five extended-spectrum beta-lactamase (ESBL)-producing were identified a cohort 1,885 French children over 5-year period. They sequenced characterize CTX-M-27 recently emerging France. (n = 17), particularly those 14),...
In vitro experimental evolution has taught us many lessons on the molecular bases of adaptation. To move towards more natural settings, in mice gut been successfully performed. Yet, these experiments suffered from use laboratory strains as well axenic or streptomycin-treated to maintain inoculated strains. circumvent limitations, we conducted a one-year vivo using isolate E. coli, strain 536, conditions mimicking much possible environment with mother-to-offspring microbiota transmission....
Fosfomycin resistance in Escherichia coli results from chromosomal mutations or acquisition of plasmid-mediated genes. Because these mechanisms may be absent some resistant isolates, we aimed at decipher the genetic basis fosfomycin E. coli. Different groups isolates were studied: fosfomycin-resistant mutants selected vitro CFT073 (MIC=1 mg/L) and two (wildtype non-wildtype) clinical isolates. Single-nucleotide allelic replacement was performed to confirm implication novel into resistance....
Little is known about the dynamics of adaptation in acute bacterial infections. By sequencing multiple isolates from monoclonal extraintestinal Escherichia coli infections several patients, we were able to uncover traces selection taking place at short time scales compared chronic infection.
Mecillinam is recommended in France as a first-line treatment for lower urinary tract infections, due to the large increase resistance of Escherichia coli other oral treatments, such co-trimoxazole or fluoroquinolones, its limited impact on faecal microbiota and stability presence numerous β-lactamases. However, we recently identified several mecillinam-resistant E. isolates with high-level expression penicillinase (HEP) phenotype that merit further study.We studied two isogenic clinical...
Due to their rapid evolution and impact on healthcare, beta-lactamases, protein degrading beta-lactam antibiotics, are used as generic models of evolution. Therefore, we investigated the mutation effects in two distant TEM-1 CTX-M-15. Interestingly, found a site with complex pattern genetic interactions. Mutation G251W inactivates protein's function, just reciprocal mutation, W251G, does The phylogenetic analysis revealed that G has been entrenched TEM-1's background: while rarely observed...
Abstract The distribution of fitness effects new mutations is central to predicting adaptive evolution, but observing how it changes as organisms adapt challenging. Here we use saturated, genome-wide insertion libraries quantify the changed in two E. coli populations that adapted a constant environment for 15,000 generations. proportions neutral and deleterious remained constant, despite large gains. In contrast, beneficial fraction declined rapidly, approximating an exponential...
Multiresistance plasmids belonging to the IncI incompatibility group have become one of most pervasive plasmid types in extended-spectrum beta-lactamase-producing Escherichia coli animal origin. The extent burden imposed on bacterial cell by these seems modulate emergence "epidemic" plasmids. However, vivo data natural environment strains are scarce. Here, we investigated cost a blaCTX-M-1-IncI1 epidemic commensal E. strain, UB12-RC, before and after oral inoculation 15 6- 8-week- old...
Abstract Epistasis affects genome evolution together with our ability to predict individual mutation effects. The mechanistic basis of epistasis remains, however, largely unknown. To quantify and better understand interactions between fitness-affecting mutations, we focus on a 11 amino-acid α-helix the protein β-lactamase TEM-1, build comprehensive library more than 15,000 double mutants. Analysis growth rates these mutants shows pervasive epistasis, which can be explained by non-linear...
Abstract Our ability to predict the impact of mutations on traits relevant for disease and evolution remains severely limited by dependence their effects genetic background environment. Even when molecular interactions between genes are known, it is unclear how these translate organism-level alleles. We therefore characterized interplay environmental dependencies in determining fitness quantifying ~4,000 expression variants two metabolic genes, different environments. detect a remarkable...
Abstract: Due to their rapid evolution and impact on health care, be-ta-lactamases, protein degrading beta-lactam antibiotics, are used as generic model of evolution. Therefore, we investigated the mutation effects in two distant beta-lactamases TEM-1 CTX-M-15. Interestingly found a site with complex pattern genetic interactions. Mutation G251W is in-activating protein’s function just reciprocal W251G CTXM-15. Phylogenetic analysis revealed that G has been entrenched background:...
Summary Objective Whole genome sequencing (WGS) of extended-spectrum β-lactamase-producing Escherichia coli (ESBL- E. ) in developing countries is lacking. Here we describe the population structure and molecular characteristics ESBL- faecal isolates rural Southern Niger. Methods Stools 383 healthy participants were collected among which 92.4% carriers; 90 these containing stools (109 isolates) further analysed by WGS, using short- long-reads. Results Most belonged to commensalism-adapted...
Background: Data on extended-spectrum β--lactamase-producing Escherichia coli (ESBL- E. coli) carriage in community settings, especially developing countries, are scarce. Here, we describe the population structure and molecular characteristics of resistance ESBL- faecal isolates a rural African population.Methods: Between April May 2017, stools 383 healthy participants were collected from 20 villages Southern Niger during clinical trial ciprofloxacin prophylaxis carried out meningococcal...
Abstract Epistasis affects genome evolution together with our ability to predict individual mutation effects. The mechanistic basis of epistasis remains, however, largely unknown. To quantify and better understand interactions between fitness-affecting mutations, we focus on a 11 amino-acid α-helix the protein β-lactamase TEM-1, build comprehensive library more than 15,000 double mutants. Analysis growth rates these mutants shows pervasive epistasis, which can be explained by non-linear...