Many infections contracted in hospital are linked to the formation of biofilms. How do these sticky layers of bacteria form on the surface of some medical devices? Can we counteract them? At UCL, nanotechnologies are answering these questions.
An estimated 7% of hospitalised patients contract a nosocomial illness during their hospitalisation. These infections can be formidable, especially when the patient’s immune system is weak and/or the responsible pathogenic bacterium resists antibiotics,1 as is the case with some types of staphylococcus aureus. In general, these bacteria, whose presence on our skin and in our mucous is normal, aren’t harmful, but they become so when they penetrate our bodies via a medical device.
What is biofilm?
Indeed, bacteria such as staphylococcus aureus can attach themselves to medical device surfaces (catheter, biomaterials, etc.). Then they multiply and form what are called biofilms, multicellular communities that can cause nosocomial infections that are especially difficult to treat because biofilms make their bacteria even more resistant to antibiotics. This can entail grave complications for the patient, which is why it’s so important to study bacterial biofilms and find a way to prevent their formation.
A super microscope
In science, a lot of knowledge comes from observation. Since a bacterium is a cell, and therefore invisible to the naked eye, a microscope is necessary. Proteins are even smaller. ‘The size of a protein is measured in nanometres, or one million times shorter than a millimetre’, says Prof. Yves Dufrêne, a bioengineer and FNRS Research Director at the UCL Institute of Life Sciences. ‘Suffice it to say that for a long time, nobody was able to observe the cell and its components via normal magnification. We had to wait for nanotechnology and the invention of the atomic force microscope, in 1986, to be able to examine life at nanoscale.’ Prof. Dufrêne’s team uses an AFM to study yeasts and bacteria, including the well-known staphylococcus aureus. Researchers analysed certain proteins on the surface of bacteria that are responsible for attaching the latter to human tissue or biomaterials.
An estimated 80% of nosocomial diseases are linked to biofilm formation. Prof. Dufrêne’s team wanted to understand the first step of biofilm formation: How do bacteria stick to each other?
Thanks to the AFM, UCL researchers, in collaboration with Irish and Italian colleagues, discovered the role played by a particular protein on the surface of staphylococcus aureus: SasG. ‘When in the presence of zinc, SasG acts a bit like a drop of glue, or like a strip of Velcro that attaches to neighbouring bacteria. Little by little, these bacteria form a bacterial community that becomes a biofilm.’
Towards anti-adhesion treatments?
This discovery was the subject of an article in a prestigious American scientific review.2 Above all, it opened the way to possible anti-adhesion treatments. ‘If we found a molecule capable of preventing SasG from sticking,’3 Prof. Dufrêne says, ‘we could prevent bacteria from sticking to each other and forming biofilms. Such anti-adhesion substances exist. For example, cranberry juice is known to prevent urinary infections because it contains a substance that prevents E. Coli, the bacterium that causes them, from sticking to the urethra and bladder walls. So it’s possible!’
From this perspective, the AFM and live-cell nanoscopy could make it possible to test and select the most anti-adhesive molecules. ‘Eventually,’ Prof. Dufrêne says, ‘maybe we’ll be able to establish preventive treatments that block biofilm formation and/or complement the antibiotic arsenal in case of bacterial infection.’
(1) See article on antibiotic resistance (lien hypertexte ?). (2) C. Formosa-Dague et al., ‘Zinc-dependent mechanical properties of Staphylococcus aureus biofilm-forming surface protein SasG’, PNAS, 2015. (3) SasG is not the only target of researchers. In all, at least a dozen proteins are responsible for staphylococcus aureus biofilm formation. Prof. Dufrêne’s research is financed primarily by the FNRS, UCL, the WELBIO programme and the ERC.