Fundamental Research Division
The DRF at the CEA assemble approximately 6,000 scientists since January 2016.
Scientific result | Structural biology | Antibiotics
Some bacteria have the ability to aggregate in order to protect themselves from the external environment, by forming colonies called biofilms. The formation of these biofilms can cause certain nosocomial infections in hospitals, for example when they are found on instruments (probes, implants, etc.); they can also cause antibiotic resistance, by promoting the appearance of more virulent mutants. Biofilms are characterized by the presence of an extracellular matrix composed of polysaccharides, DNA and amyloid fibers. This matrix makes biofilms resistant to antibiotic treatments and allows bacteria to communicate chemically, in a form of communication known as quorum sensing.
But how does quorum sensing work in the very early stages of biofilm formation when bacterial density is low and no matrix has yet been formed? By combining several structural biology approaches, researchers from the IBS in collaboration with the Université de la Méditerranée in Marseille and Jacobs University in Bremen (Germany), discovered that Providencia stuartii, a bacterium frequently isolated in burn patients and people under long-term catheterization (i.e. retirement homes and hospitals), establishes intercellular communication directly at the planktonic stage – that is, before the secretion of an extracellular matrix. They observed that P. stuartii forms floating cellular communities within which the cells are in direct contact, before settling in the form of biofilms. Assuming that this contact necessarily involves proteins from the outer membrane, and that they must be abundant to allow the tight fastening observed within floating communities, the researchers crystallized two P. stuartii proteins, called porins, corresponding to 70% of the protein content of the outer membrane, and resolved their structures with atomic resolution by X-ray crystallography.
It turns out that the porins are assembled in the form of trimers, or "trios" of porins. Porin channels within these trios are open and face each other, suggesting that they can allow direct chemical communication between adjacent cells within the floating communities. This mechanism could be adapted to intercellular communication even at very low cell density, and therefore in the first stages of biofilm formation – namely, when it is still vulnerable to attack. This discovery identifies porins as new targets in the fight against biofilms and could make way for the development of innovative therapies.
Porin self-association enables cell-to-cell contact in Providencia stuartii floating communities | PNAS
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.