Understanding how a commensal bacterium becomes drug resistant through horizontal gene transfer is a central issue in microbiology.
Using a combination of molecular genetics and live-cell imaging (fluorescence microscopy with microfluidics), we visualize cell-to-cell DNA transfer by conjugation and the subsequent establishment of drug resistance in the recipient bacterium.
All the same but not equal.
Microscopy of E. coli clonal population upon tetracycline treatment shows anti-correlation between the intracellular levels of Tetracycline (in green) versus the efflux pump protein TetA (in red), and reveals cell-to-cell heterogeneity.
The lab investigates both vertical and horizontal DNA transfer in bacteria. We use a combination of molecular genetics and microscopy imaging to observe the real-time dynamics of proteins and DNA in live bacterial cells.
During vertical DNA transfer, genetic material is faithfully transmitted from mother to daughter cells. We study the main DNA repair mechanisms, homologous recombination, which safeguards the integrity of the transmitted genetic information in all living organisms. What we learn from bacteria serves as a paradigm to better understand genetic instability responsible of genetic diseases and cancers.
We also focus on horizontal DNA transfer, which is responsible for the dissemination of multi-drug resistance between bacterial species. We investigate the dynamics of transfer from one cell to the other by direct contact, as well as the subsequent establishment of effective drug resistance.
Horizontal DNA transfer and the spread of drug resistance:
Understanding how a commensal bacterium becomes drug resistant through horizontal gene is a central issues in Microbiology. One way to address these questions is to use a combination of molecular genetics and microscopy imaging in live cells, which has proven to be a powerful strategy to gain insight into biological processes. Recent high-resolution imaging techniques, in particular Structured-Illumination Microscopy (SIM), enable us to observe the real-time dynamics of proteins or DNA sequences with unprecedented resolution. Live cell imaging technic is combined with specifically developed sample preparation and microfluidics apparatus that allow observation of cells growing under physiological conditions over several generations. Hence, fundamental mechanisms that previously have only been characterised through genetic or biochemical studies can now be investigated in the context of the living cell.
We then study the acquisition of DNA by bacterial conjugation at the cytological scale. Conjugation is the major process involved in the acquisition of exogenous DNA and associated new properties such as pathogenesis or multidrug resistance. Translating our molecular knowledge of conjugation mechanisms to an in vivo context is currently the biggest challenge in the field and is the main objective of our research. To tacle these questions, we have developed a genetic system that enables the microscopic visualization of each key steps of DNA conjugation in live cells, i.e., DNA transfer from donor to recipient cells, maintenance of the acquired DNA and expression of newly acquired gene in the transconjugant cells and consequent establishment of new properties, such as resistance to antibiotics. In particular, we study the dynamics of acquisition of a tetracycline-resistance-carrying plasmid in order to characterise the chronology of conversion of commensal bacterium into a drug resistant cell.
• Since 2015: Group leader INSERM-CNRS at MMSB-UMR5086, Cell-to-cell DNA transfer. Funding: ATIP-Avenir CNRS-INSERM, FINOVI, FRM
• 2009-2015: Bacterial chromosome biology (Research associate), Prof. DJ Sherratt (Bioch Dept. University of Oxford). Funding: EMBO Long Term Fellowship and The Welcome Trust
• 2006-2009: Segregation and stability of the bacterial chromosome (Research associate), Boccard F. PhD (CNRS-CGM Paris, France). Funding: National Agency for Research (A.N.R.)
• 2005: Academic Visitor in Santanu Dasgupta Lab (BMC-Uppsala University Sweden), Cell cycle impairment due to chromosome disruption in Escherichia coli. Funding: EMBO Short-Term Fellowship; F.E.M.S, A.T.U.P.S Paul Sabatier
• 2001-2005: Ph.D in Molecular genetics and microbiology, Organisation and segregation of the Escherichia coli chromosome, Cornet F. PhD. and Prof. Louarn JM. University of Toulouse (LMGM-CNRS Toulouse France). Funding: French Minister of Research and Education
• Médaille des grandes avancées Françaises en biologie (Académie des sciences - AXA), 2015
• Biochemistry dept. Excellence Award - Oxford University, 2015
Meeting with high school students during the Déclics 2017 event.
Déclics Captain at the du Parc high school, in Lyon.
Dec 2017, Cercle FSER event
Visiting primary school Jules Ferry – Oullins: Microbiology for kids
June 2016, Methods Mol Biol
Aug 2015, Proc Natl Acad Sci U S A.