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, see also FNRS News in FR, 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 ( https://futurumcareers.com/using-nanotechnology-to-overcome-the-adhesion-of-the-bacterial-pathogen-staphylococcus-aureus).
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.
September 1, 2021
A protein complex involved in pathogen adhesion ruptures at 3 nanonewtons !
Staphylococci bind to the blood protein von Willebrand Factor (vWF), thereby causing endovascular infections. Whether and how this interaction occurs with the medically important pathogen Staphylococcus epidermidis is unknown. Using single-molecule experiments, we demonstrate that the S. epidermidis protein Aap binds vWF via an ultrastrong force of about 3 nN, the strongest noncovalent biological bond ever reported, and we show that this interaction is activated by tensile loading, suggesting a catch-bond behavior. Our results published in Nano Lett. point to a mechanism where force-induced unfolding of the B repeats activates the A domain of Aap, shifting it from a weak- to a strong-binding state, which then engages into an ultrastrong interaction with vWF A1. This shear-dependent function of Aap offers promise for innovative antistaphylococcal therapies.
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 a study published in Nanoscale Horizons , 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".
June 4, 2020
Fast chemical force microscopy reveals hydrophobic nanodomains on mycobacteria
In a new study published in Nanoscale Horizons, we show that fast quantitative imaging (QI) AFM combined with hydrophobic tips is a powerful tool to quantitatively map hydrophobic properties of bacterial pathogens, at high spatiotemporal resolution (∼10 min for 128 × 128 pixels images). We focus on Mycobacterium abscessus, a multidrug-resistant bacterial pathogen causing severe lung infections in cystic fibrosis patients. We discover that the transition from a smooth to a rough colony morphology, caused by the loss of cell envelope associated glycopeptidolipids (GPLs), leads to a dramatic change in surface hydrophobicity, smooth bacteria displaying unusual nanodomains with varying degrees of hydrophobicity. These results show that GPLs modulate the nanoscale distribution of hydrophobicity of M. abscessus, which is critical for regulating bacterial adhesion and aggregation, as well as virulence and pathogenicity. This study demonstrates the power of QI-AFM as a nanoimaging tool for probing the hydrophobic properties of cell surfaces in relation to function, at high speed and spatial resolution.
April 14, 2020
Mechanobiology: what makes bacterial pathogens so stiff?
Bacteria are surrounded by mechanically rigid cell envelopes, which play important roles in controlling cellular processes like growth, division, adhesion as well as resistance to drugs and environmental stresses. In the prototypical pathogen Escherichia coli, it has long been believed that peptidoglycan was the only biopolymer that conveys mechanical strength to the cell envelope. However, in a study published in Nature Communications, the teams of Yves Dufrêne and Jean-François Collet (WELBIO investigator) at the UCLouvain have identified the key roles of the lipoprotein Lpp in defining the E. coli cell envelope mechanics, using state-of-the-art nanoimaging techniques combined with genetic manipulation. They discovered that Lpp has a dual function, by covalently connecting peptidoglycan to the outermost cellular membrane and by precisely tuning the size of the periplasmic space. The researchers also found that Lpp-dependent cell mechanics has a major impact on antibiotic sensitivity, functional mutations in the protein increasing drastically the efficacy of vancomycin. This study, funded by the Excellence of Science (EOS), WELBIO and ERC fundings, demonstrates the power of coupling nanotechnology and molecular biology methods for understanding the molecular details behind bacterial stiffness, and for linking cellular mechanics to function, a grand challenge in current mechanobiology. The results show promise for the design of innovative antibacterial drugs targeting the molecular machineries that stabilize the cell envelope.
See the Nature Microbiology blog for more details.
See Daily Science
January 20, 2020
Mechanomicrobiology: how bacteria sense and respond to forces
Microorganisms have evolved to thrive in virtually any terrestrial and marine environment, exposing them to various mechanical cues mainly generated by fluid flow and pressure as well as surface contact. Cellular components enable bacteria to sense and respond to physical cues to optimize their function, ultimately improving bacterial fitness. Owing to newly developed biophysical techniques, we are now starting to appreciate the breadth of bacterial phenotypes influenced by mechanical inputs: adhesion, motility, biofilm formation and pathogenicity. In this Nature Reviews Microbiology, with the Alex Persat team, we discuss how microbiology and biophysics are converging to advance our understanding of the mechanobiology of microorganisms.
September 18, 2019
How strong is the fibrinogen bridge between staphylococcal surface protein ClfA and endothelial cell integrin aVb3 ?
Binding of the Staphylococcus aureus surface protein clumping factor A (ClfA) to endothelial cell integrin aVb3 plays a crucial role during sepsis, by causing endothelial cell apoptosis and loss of barrier integrity. ClfA uses the blood plasma protein fibrinogen (Fg) to bind to aVb3, but how this is achieved at the molecular level is not known. In a Nano Lett paper we demonstrate that the ClfA-Fg-aVb3 ternary complex is extremely stable, being able to sustain forces (∼800 pN) that are much stronger than those of classical bonds between integrins and the Arg-Gly-Asp (RGD) tripeptide sequence (∼100 pN). Our experiments favor a binding mechanism involving the extraordinary elasticity of Fg. In the absence of mechanical stress, RGD sequences in the Aa chains mediate weak binding to aVb3, whereas under high mechanical stress, exposure of cryptic Aa chain RGD sequences leads to extremely strong binding to the integrin.
May 26, 2019
ISPM 2019
Owing to David and the team we hosted ISPM 2019 which was a real success !
See the following video by Mervyn Miles https://youtu.be/fqi2vzdSOKc
April 30, 2019
Fluidic force microscopy captures amyloid bonds between yeast cells
Congrats to Jérôme et al., including P. Lipke (New York Brooklyn College), for measuring the forces driving Als5-mediated intercellular adhesion in Candida albicans, using an innovative fluidic force microscopy platform (Nano Lett). The results point to a model whereby amyloid-like β-sheet interactions play a dual role in cell-cell adhesion, that is, in formation of adhesin nanoclusters ( cis-interactions) and in homophilic bonding between amyloid sequences on opposing cells ( trans-interactions). Because potential amyloid-forming sequences are found in many microbial adhesins, we speculate that this novel mechanism of amyloid-based homophilic adhesion might be widespread and could represent an interesting target for treating biofilm-associated infections. This new methodology is also discussed in Trends Microbiol. (2019, 27(9):728-730).
April 30, 2019
Staphylococcus aureus protein A binding to von Willebrand factor is activated by force
Protein A (SpA) binds to von Willebrand factor (vWF) under flow, but the molecular basis of this stress-dependent interaction has not yet been elucidated. Congrats to Felipe and our collaborators at the University of Pavia who have shown that the SpA-vWF interaction is regulated by a new force-dependent mechanism. This study published in mBio highlights the role of mechanoregulation in controlling the adhesion of S. aureus and shows promise for the design of small inhibitors capable of blocking colonization under high shear stress.
November 1, 2018
Atomic force microscopy-based mechanobiology
Mechanobiology describes how biological systems respond to mechanical stimuli. In a Nature Reviews Physics review paper, together with several experts in the field, the nBio team survey the basic principles, advantages and limitations of applying and combining atomic force microscopy-based modalities with complementary techniques to characterize the morphology, mechanical properties and functional response of complex biological systems to mechanical cues.
https://www.nature.com/articles/s42254-018-0001-7
September 12, 2018
Bacterial sexuality at the nanoscale
With the Mahillon team we introduce an innovative atomic force microscopy platform to study and mechanically control DNA transfer between single bacteria, focusing on the large conjugative pXO16 plasmid of the Gram-positive bacterium Bacillus thuringiensis, a study published in Nano Lett. This technology may enable researchers to mechanically control gene transfer among a wide range of Gram-positive and Gram-negative bacterial species and to understand the molecular forces involved.
August 14, 2018
Staphylococcus aureus and eczema: a nanoscale view
Bacterium-skin interactions play important roles in skin disorders, yet their molecular details are poorly understood. In a paper published in mBio, we and our collaborators in Ireland decipher the molecular forces at play during adhesion of Staphylococcus aureus to skin corneocytes in the clinically important context of atopic dermatitis, also known as eczema. We identify a unique relationship between the level of natural moisturizing factor in the skin and the strength of bacterium-corneocyte adhesion. Bacterial adhesion is primarily mediated by the surface protein clumping factor B and is enhanced by physical stress, highlighting the role of protein mechanobiology in skin colonization. Similar to a catch bond behavior, this mechanism represents a promising target for the development of novel antistaphylococcal agents.
May 7, 2018
Mechanobiology: Staphylococcus aureus under tension !
Staphylococcus aureus is an important bacterial pathogen which is a leading cause of biofilm-associated infections on indwelling medical devices. Biofilms are currently estimated to be involved in more than 65 % of hospital-acquired infections. There is evidence that bacterial adhesion and biofilm formation are favored under high physical stress, but how this is achieved at the molecular level is not known. In a study published in PNAS, our team, together with the Trinity College Dublin, has elucidated the mechanism by which S. aureus responds to mechanical tension. We focused on the bacterial surface protein ClfA, and on its interaction with fibrinogen, a blood protein that rapidly covers implanted medical devices. Using atomic force microscopy, we showed that ClfA behaves as a force-sensitive molecular switch that potentiates staphylococcal adhesion under mechanical stress. The adhesion of ClfA is weak at low tensile force, but is dramatically enhanced by mechanical tension, as observed with catch bonds. Strong bonds are inhibited by a peptide mimicking Fg, which offers prospects for the development of antiadhesion therapeutics. These findings are of biological significance because they explain at the molecular level the ability of ClfA to promote bacterial attachment under high physiological shear stress. This study emphasizes the role of mechanobiology in staphylococcal biofilms, a topic that we also discusses in a recent perspective article in Science.
For more details, see https://uclouvain.be/fr/sciencetoday/actualites/le-stress-du-staphylocoque-dore.html
April 24, 2018
New ACS Nano paper: Mechanical forces guiding Staphylococcus aureus cellular invasion
Invasion of mammalian cells by S. aureus involves fibronectin-dependent bridging between FnBPs on the bacterial surface and α5β1 integrins in the host cell membrane, but the fundamental forces involved are poorly understood. With our colleagues from the University of Pavia, we have used state of the art single-cell and single-molecule experiments to quantify the molecular forces engaged in this three component interaction, revealing that the fibronectin bridge between FnBPs and the α5β1 integrin is mechanically strong.
March 30, 2018.
New perspective article in Science: Force matters in hospital-acquired infections
Building up on an outstanding paper by Gaub et al. we discuss how extremely strong forces help staphylococci to colonize biomaterials and infect humans.
December 5, 2017.
Physical stress activates the adhesive function of Staphylococcus aureus surface protein clumping factor B
Staphylococcus aureus colonizes the skin and the nose of humans and can cause various disorders, including superficial skin lesions and invasive infections. During nasal colonization, the S. aureus surface protein clumping factor B (ClfB) binds to the squamous epithelial cell envelope protein loricrin, but the molecular interactions involved are poorly understood. In a new paper published in mBio, we unravel the molecular mechanism guiding the ClfB-loricrin interaction. We show that the ClfB-loricrin bond is remarkably strong, consistent with a high affinity "dock, lock and latch" binding mechanism. We discover that the ClfB-loricrin interaction is enhanced under tensile loading, thus providing evidence that the function of a S. aureus surface protein can be activated by physical stress.
September 1-15, 2017.
Pr. Peter Lipke is visiting us
We are honered to host Pr. Peter Lipke (CUNY Brooklyn, USA), world expert in yeast biofilms and longstanding collaborator, for a sabbatical stay. You can see him here learning the basics of AFM with Philippe.
September 5, 2017.
How fibrinogen activates the capture of human plasminogen by staphylococcal surface proteins
Invasive bacterial pathogens can capture host plasminogen and allow it to form plasmin, a process of medical importance as surface-bound plasmin promotes bacterial spreading by cleaving tissue components and favours immune evasion by degrading opsonins. Together with the Speziale and Foster teams, we discovered that Staphylococcus aureus fibronectin-binding proteins bind plasminogen by a sophisticated activation mechanism involving fibrinogen, another ligand found in the blood. The work has just been published in mBio.
June 20, 2017.
Imaging the growth of a bacterial functional amyloid at single-fiber resolution
Amyloids are aggregative protein fibrils best known for their implication in degenerative illnesses such as Alzheimer’s and Parkinson’s diseases. However, microbes can also produce so-called functional amyloids, i.e. amyloids that serve a dedicated biological function. Curli are functional amyloids produced by Escherichia coli as part of the extracellular matrix that holds cells together into biofilms. The molecular events that occur during curli nucleation and fiber extension remain largely unknown. A team of scientists from the VIB lab of Han Remaut (VIB-VUB) and our lab collaborated on a study published in Nat Chem Biol (lien: https://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.2413.html), in which high speed atomic force microscopy was used to film the formation of curli fibers in real-time and at high resolution, revealing new insights into curli nucleation and growth.
April 6, 2017.
New review in Nat Nanotechnol on AFM imaging modes
Together with colleagues in the field, we review the basic principles, advantages and limitations of the most common AFM bioimaging modes, including the popular contact and dynamic modes, as well as recently developed modes such as multiparametric, molecular recognition, multifrequency and high-speed imaging. For each of these modes, we discuss recent experiments that highlight their unique capabilities.
March 21, 2017.
Discovery of a peptide capable to prevent biofilm formation by Staphylococcus aureus
S. aureus has an exceptional ability to stick to implanted biomaterials, such as central venous catheters and prosthetic joints, leading to the formation of biofilms. Biofilm-related infections are difficult to eradicate because bacterial cells are protected from host defenses and are resistant to many antibiotics. An attractive alternative to antibiotics is the use of antiadhesion compounds to block bacterial adhesion and biofilm development. In collaboration with Timothy Foster and Joan Geoghegan (Trinity College Dublin), an ISV team identified a peptide capable of preventing the formation of S. aureus biofilms. They first unravelled the molecular interactions by which the surface adhesin SdrC mediates biofilm accumulation. SdrC was found to mediate cell-cell adhesion through weak homophilic bonds, and to also promote strong hydrophobic interaction with inert surfaces. They discovered that a peptide derived from the neuronal cell adhesion molecule β-neurexin is able to inhibit SdrC-dependent attachment to inert surfaces, cell-cell adhesion, and biofilm formation. These findings, published in PNAS raise the possibility that the peptide could be used as a platform for designing a peptidomimetic with potential to prevent biofilm infections.
February 2, 2017.
Congrats to Claire and Valeria for their new paper in ACS Nano.
While it is established that the collagen-binding protein Cna from Staphylococcus aureus binds to collagen via the high-affinity collagen hug mechanism, whether this protein is engaged in other ligand-binding mechanisms is poorly understood. Here, we use atomic force microscopy to demonstrate that Cna mediates attachment to two structurally and functionally different host proteins, i.e., the complement system protein C1q and the extracellular matrix protein laminin, through binding mechanisms that differ from the collagen hug. Both C1q and laminin interactions can be efficiently blocked by monoclonal antibodies directed against the minimal binding domain of Cna.
January 12, 2017.
New ACS Nano perspective article: Microbial Nanoscopy: Breakthroughs, Challenges, and Opportunities.
microbial nanoscopy janvier 2017
October 26, 2016.
Congrats to Philippe and Claire for their new mBio paper.
Together with the Speziale and Foster teams, we unravel the mechanical strength of the Staphylococcus aureus Cna adhesion protein in living bacteria. We show that single Cna-collagen bonds are very strong, reflecting high-affinity binding by the collagen hug mechanism. We discover that the B region behaves as a nanospring capable of sustaining high forces. This unanticipated mechanical response, not previously described for any staphylococcal adhesin, favors a model in which the B region has a mechanical function that is essential for strong ligand binding. Finally, we assess the antiadhesion activity of monoclonal antibodies against Cna, suggesting that they could be used to inhibit S. aureus adhesion.
October 26, 2016.
New review in Nature Microbiol.
Together with the Xiao team from The Johns Hopkins School of Medicine (USA), we discuss the principles, advantages and limitations of the main optical and force nanoscopy techniques available in microbiology, and we highlight some outstanding questions that these new tools may help to answer.
May 10, 2016.
New paper in Nanoscale Horizons.
The human skin is colonized by a wide diversity of microorganisms, including bacterial, fungal and virus species. Although most skin colonizers are harmless or beneficial, some of them like Staphylococcus aureus can be implicated in skin disorders. So far, direct measurement of the molecular forces involved in microbe-skin interactions has not been possible. In a new study with the Staphylococcal research group (Trinity College Dublin, Ireland), we developed a novel nanoscopy technique combining multiparametric atomic force microscopy with single bacterial probes, that enables us to provide spatially-resolved quantitative maps of bacterial–host adhesion on skin surfaces. The method could be used to advance our knowledge of S. aureus adhesion to corneocytes from children with eczema. More broadly, it should find broad utility for studying the molecular basis of host–microbe interactions.
See also news in Chemistryworld: AFM maps bacteria on skin.
April 14, 2016.
New ERC grant NanoStaph.
Yves receives an Advanced Grant from the European Research Council (ERC) to explore staphylococcal biofilms using the new tools of nanotechnology. Staphylococcus aureus is a leading cause of hospital-acquired infections, which are often complicated by the ability of this pathogen to grow as biofilms on indwelling medical devices. Because biofilms protect the bacteria from host defenses and are resistant to many antibiotics, biofilm-related infections are difficult to fight and represent a tremendous burden on our healthcare system. Today, a true molecular understanding of the fundamental interactions driving staphylococcal adhesion and biofilm formation is lacking owing to the lack of high-resolution probing techniques. This knowledge would greatly contribute to the development of novel antiadhesion therapies for combating biofilm infections. This multidisciplinary project aims at developing innovative atomic force microscopy (AFM) techniques in biofilm research, enabling us to understand the molecular mechanisms of S. aureus adhesion in a way that was not possible before, and to optimize the use of anti-adhesion compounds capable to inhibit biofilm formation by this pathogen.
