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 19, 2023
Tuberculosis: sweet nanodomains on the pathogen surface help it escape our immune system
By combining the tools of nanotechnology and microbiology, the teams of Yves Dufrêne (FNRS, UCLouvain) and Jérôme Nigou (CNRS) have unraveled the sophisticated mechanism by which mycobacterial pathogens causing tuberculosis evade the immune system of the human host. In the future, these findings may help designing new anti- tuberculosis strategies.
The bacterial pathogen Mycobacterium tuberculosis, the causative agent of human tuberculosis kills a million people each year. New molecular knowledge on the infection process is urgently needed in order to develop better anti-mycobacterial therapies. To protect us from the pathogen, our immune cells are decorated with a family of proteins called pattern recognition receptors, of which the well-known DC-SIGN protein binds specific sugars (glycoligands) on the mycobacterial cell surface. Remarkably, mycobacteria have evolved ways to use this interaction to their own benefit, enabling them to escape the body’s immune system. While we know the structures of the exotic molecules involved and how they react at the population level in the test tube, we know little about how they bind in real life on the surfaces of immune cells. Using state-of-the-art atomic force microscopy, the researchers were able to map the distributions of glycoligands and DC-SIGN receptors with unprecedented single-molecule resolution. These molecular recognition imaging experiments demonstrated for the first time that glycoligands are concentrated into dense nanoscale domains on the mycobacterial surface. In addition, adhesion of bacteria to host cells was shown to induce the formation of large DC-SIGN clusters on immune cells. This study, published in Science Advances, highlights the key role of nanoclustering of both pathogen ligands and DC-SIGN host receptors, which is only possible to analyse through super-resolution, nanoscopy techniques. This fascinating mechanism might be widespread in pathogen-host interactions and may help designing new antituberculous strategies using immunomodulation.
September 1, 2022
In a study based from Scopus of the top researchers among all scientific disciplines, Stanford University ranks us #8,451 from a pool of 10 M scientists (i.e. ~0.08 %). The database provides standardized information on citations, h-index, co-authorship adjusted hm-index, citations to papers in different authorship positions and a composite indicator (c-score).
May 9, 2022
Adhesion of Staphylococcus aureus to human skin is exceptionally strong
Staphylococcus aureus is a bacterial pathogen that colonizes the skin and the nose of humans, and which can cause various diseases, such as eczema (atopic dermatitis). This microbe has become resistant to multiple antibiotics, meaning there is an urgent need to fully understand the molecular mechanisms leading to host colonization and infection, and to find alternative antibacterial therapies. In collaboration with the Trinity College Dublin, a UCLouvain team has discovered that S. aureus uses a special surface protein, FnBPB, to specifically bind to the human skin surface protein loricrin. Using nanotechniques, they found that the bond formed between FnBPB and loricrin is exceptionally strong, much stronger than the vast majority of other biomolecular bonds. Remarkably, the bond strength increases dramatically when subjected to physical stress, as occurring when we wash ourselves or during skin epidermidis turnover, pointing to an unusual "catch bond" adhesion and colonization mechanism. Under mechanical tension, biological complexes typically slip apart easily ("slip bonds"), whereas "catch bonds" counterintuitively become stronger. The FnBPB-loricrin interaction, reported in Nature Communications, provides S. aureus with a means to firmly attach to the epidermidis under physiological shear stress, increasing its ability to colonize the human skin and cause infection. This mechanism represents a promising target for anti-adhesion therapy, i.e. the design of inhibitors capable to efficiently prevent staphylococcal-skin interactions. The study was funded by an ERC advanced grant aiming at using nanotechnology to understand and overcome the adhesion of S. aureus to biomaterials and host tissues ( ).
September 23, 2021
New methods review: AFM force spectroscopy of single cells
Physical forces and mechanical properties have critical roles in cellular function, physiology and disease. Over the past decade, atomic force microscopy (AFM) techniques have enabled substantial advances in our understanding of the tight relationship between force, mechanics and function in living cells and contributed to the growth of mechanobiology. In the new journal Nat Rev Methods, the nBio group publishes together with two other teams a comprehensive overview of the use of AFM-based force spectroscopy (AFM-FS) to study the strength and dynamics of cell adhesion from the cellular to the single-molecule level, spatially map cell surface receptors and quantify how cells dynamically regulate their mechanical and adhesive properties. We first introduce the importance of force and mechanics in cell biology and the general principles of AFM-FS methods. We describe procedures for sample and AFM probe preparations, the various AFM-FS modalities currently available and their respective advantages and limitations. We also provide details and recommendations for best usage practices, and discuss data analysis, statistics and reproducibility. We then exemplify the potential of AFM-FS in cellular and molecular biology with a series of recent successful applications focusing on viruses, bacteria, yeasts and mammalian cells. Finally, we speculate on the grand challenges in the area for the next decade.