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.
