Postal Address :
Croix du Sud, 4-5
E-mail : Yves Dufrêne
Tel. +32 10 47 36 00
Secretariat +32 10 47 35 88
Carnoy Bldg (SC12)
Floor 04, room C455
Microbiology at the nanoscale
Our goal is to push the limits of force nanoscopy beyond state-of-the-art to establish this nanotechnology as an innovative platform in biofilm research. By developing new tools, we wish to understand how pathogens use their surface molecules to guide cell adhesion and trigger infections, and to develop anti-adhesion strategies for treating biofilm-infections.
"Knowledge is limited. Imagination encircles the world.” ― A. Einstein
May 13, 2021
AFM force-clamp spectroscopy captures the nanomechanics of the Tad pilus retraction
Bacterial pili are flexible and dynamic nanofilaments that fulfil a wealth of cellular functions. In this study, we investigated the nanomechanics and dynamics of Tad pilus retraction, using a platform combining a fluorescence-based piliated cell discrimination assay with atomic force microscopy (AFM) force-clamp spectroscopy. We discover that applying a constant tensile load to single pili connected to hydrophobic substrates leads to two types of transient variations in force and height, originating from pilus retraction and from hydrophobic binding. These findings support a model whereby pilus retraction and hydrophobic interactions work in concert to promote bacterial cell landing on surfaces. Our experiments emphasize the power of force-clamp AFM to understand the nanophysics and dynamics of motorized bacterial pili. In nanomedicine, our methodology may provide a means to screen for small molecules that can hinder pilus retraction in bacterial pathogens, thereby helping to prevent or treat infections.
January 4, 2021
Unravelling the molecular secrets of yeast sexuality
In a paper published in Communications Biology, we and the Lipke team (USA) - use single-cell fluidic force microscopy to investigate the molecular binding mechanisms of sexual agglutinins in budding yeast Saccharomyces cerevisiae. We report that mechanical tension enhances the strength of agglutinin interactions, supporting a new model in which physical stress induces conformational changes in the binding sites of agglutinins.
October 27, 2020
Bacterial pathogens with a strong grip
During pathogenesis, bacterial pathogens adhere to host surfaces through specific receptor-ligand bonds that experience strong hydrodynamic forces. It is commonly accepted that such adhesion complexes slip apart more easily under increasing external shear ("slip bonds"). However, it has become clear that mechanical stimulation can also promote cell adhesion through "catch bonds" complexes that, counterintuitively, strengthen under force, similarly to a Chinese finger trap. Until recently microbial catch-bond mechanisms had only been identified and thoroughly characterized at the molecular level for the Escherichia coli FimH adhesion protein. The longer-lived bonds formed by FimH and mannose residues on endothelial cells eventually favor pathogen adhesion, during urinary tract infections. A recent LIBST study published in Nature Communications provides the first direct and quantitative demonstration of a catch-bond in a Gram-positive pathogen, by means of atomic force microscopy. The authors discover that the interaction between staphylococcal surface protein SpsD and fibrinogen, a crucial component of the extracellular matrix, is extremely strong and exhibits a catch binding behavior up to a critical force orders of magnitude higher than previously investigated purified complexes. This provides the pathogen with a mechanism to tightly control its adhesive function during colonization and infection, staphylococci being highly involved in vascular and skin diseases. This work, funded by ERC, improves our understanding of the molecular details behind stress-dependent bacterial adhesion and could pave the way for the development of antiadhesive therapies able to inhibit such phenomena. See also "When bacteria hang on tight".