Presentation of the team
CURRENT RESEARCH
Research addressing infection processes has recurrently overlooked the ability of genetically identical bacteria to develop, constantly and reversibly, subpopulations with distinct functionalities and physiologies. This phenomenon termed phenotypic heterogeneity is of major clinical importance as it implies the formation of persisters, rare individuals that transiently enter dormancy, stochastically or in response to stresses, thereby evading the bactericidal activities of antibiotics, causing non-resolving infection and relapse. Persisters are traditionally detected in broth, a posteriori, using population averaging methods, greatly limiting our understanding of the persisters biology during the infection. Fundamental questions remain about the capacity of the persisters to withstand both the antibiotic treatments and the bactericidal activities of the host.
Contributing to- and fostered by- the recent advances in single-cell technologies, we have been studying the biology of the persisters during the infection and antimicrobial treatment for several years. We developed an innovative single-cell based pipeline to track, collect and analyse within-host persisters that rendered important breakthroughs reachable. We are currently characterizing the processes underlying the bacterial persistence during the infection using as model organism Legionella pneumophila. It is a waterborne facultative intracellular pathogen and the agent of the Legionnaires’ disease (LD). LD is a life-threatening pneumoniae with a worrisome increase in number of cases in the European Union and for which tolerance to antibiotics and relapsing infections are clinically documented. Tackling antibiotic persistence is becoming a keystone in the fight against recalcitrant infections and the recent years have seen a rising interest in the phenomenon of persistence. Hence, our research will provide new fundamental insights regarding the pathogen phenotypic variation during the infection while contributing to answering major societal issues.
Of note, with our methodology, we can provide, with an unprecedented resolution, valuable information regarding the pathogen single-cell dynamics and the associated physiological parameters, on the bases of which new molecules and therapeutic strategies can be developed and/or evaluated. We are valorizing this approach by integrating opportunistic multidrug resistant pathogens causing ventilator-associated pneumoniae, that have been ranked by the World Health Organization as a critical priority pathogens to promote drug research and development.
At the CIRI, we benefit from an extraordinary scientific environment. It includes teams specific know-hows and models and a tight link to the clinics. In addition we have a direct access to the SFR Biosciences (UMS3444/US8), a federative structure that covers all the technological facilities necessary to conduct our research projects.
RESEARCH HISTORY
Our research has been historically sitting at the interface between medical microbiology, cell biology, and molecular biology as exemplified by our research achievements (Here). Our work relies on an innovative combination of cutting-edges single-cell techniques (flow cytometry, cell sorting, image flow cytometry, confocal microscopy, and microfluidics), omics analysis as well as classical methods in microbiology, cell biology, molecular biology, infection biology. In the recent years we have contributed to the field of bacterial phenotypic heterogeneity, persistence and virulence by investigating the single-cell dynamics of pathogen during the infection.
Our group originates from the junior group led by Nicolas Personnic at the University of Zürich (Switzerland), and sponsored by the Swiss National Foundation (Ambizione program), to study the phenotypic heterogeneity of Legionella pneumophila.