Yves Dufrêne

For students and newcomers, see this brochure in EN or FR. 

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

Latest news 

September 3, 2025

Calcium-driven ultrastrong adhesion in staphylococcal skin infection

Staphylococcus aureus colonizes the human skin, thereby causing various disorders, including eczema. Highly virulent strains that are resistant to multiple antibiotics represent a leading cause of nosocomial infections that are difficult to eradicate, emphasizing the need for alternative treatments. Attachment of S. aureus to the skin involves specific bacterial cell surface proteins that bind to target ligands on the outer surface of the epidermis. 

In a recent study published in Science Advances, research teams from Auburn University, University of Birmingham, and UCLouvain used in vitro and in silico single-molecule force spectroscopy to demonstrate that the staphylococcal serine-aspartate repeat D (SdrD) protein forms ultrastrong bonds with the skin protein desmoglein-1 (DSG-1). This is among the strongest non-covalent protein-protein interaction ever reported, explaining why the pathogen remains attached to the skin even after scratching or washing, and helping us understand why these infections are so difficult to get rid of. Remarkably, the teams discovered that calcium, an element better known for strengthening bones, plays a key role in fortifying this bacterial grip. When calcium levels are reduced, the bond between SdrD and DSG-1 weakens significantly. When calcium is added back, the bond becomes even stronger. 

This finding is particularly relevant for patients with eczema, where disrupted calcium gradients amplify SdrD interactions, which could potentially intensify S. aureus virulence. This study provides crucial insights into the calcium-dependent regulation of pathogen adhesion and opens the door to new strategies for combating antibiotic-resistant infections. Instead of trying to kill bacteria directly, which often drives the evolution of resistance, scientists could design therapies that block or weaken bacterial adhesion.

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.