31 May 2016 - PRESSE RELEASE
Weakening dangerous bacteria in biofilms
DZIF scientists at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) have succeeded in identifying and targeting problematic pathogens in biofilms more rapidly. The biofilm adhesion protein, lectin, or LecB, is suitable for rapidly diagnosing dangerous Pseudomonas strains and can be used as a target protein for treatment. The results have been published in the journal "Chemical Science".
Pseudomonas aeruginosa is a persistently challenging pathogen that causes many nosocomial infections. The bacteria produce biofilm which protects them against antibiotics, and the majority of them are additionally resistant to many antibiotics. The scientists sequenced dangerous Pseudomonas strains from clinical samples and have now identified adhesion proteins, so-called lectins, that can serve as biochemical markers. These markers permit a more rapid identification of dangerous bacterial strains and enable tailoring treatment to the patient. Although the sequences that can lead to this marker function vary substantially, the scientists demonstrated that the different types of lectins bind to comparable sugar structures. Therefore, clinically relevant Pseudomonas strains can be classified with the help of lectin sequences. At the same time, precisely the same active substance can also be used to break up the biofilm. The research work was conducted at the German Center for Infection Research (DZIF) in collaboration with the Helmholtz Centre for Infection Research (HZI) in Braunschweig and partners in Grenoble (France) and San Diego (USA).
“Lectins are protein molecules that bind different components of the biofilm to each other—the cement in a brick wall so to say,” says Dr Alexander Titz, head of a DZIF junior research group at the HIPS in Saarbrücken. “Lectins can bind to several sites on sugar molecules, such as mannose and galactose, which are found on the surface of the bacteria and host cells, and then connect them.” The researchers want to make use of these sugar molecules and chemically manipulate them to turn them into lectin inhibitors. “If we succeed in chemically disrupting the function of lectins, the biofilm components can no longer adhere to each other. The bacteria then drift away from the colony and once again become visible to the immune system and can be treated with antibiotics,” says Titz. This is the current treatment approach for pathogens that produce biofilm and their associated chronic infections, which should avoid the development of resistance due to its mechanism of action.
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The virulence factor LecB varies in clinical isolates: consequences for ligand binding and drug discovery: Roman Sommer, Stefanie Wagner, Annabelle Varrot, Corwin M. Nycholat, Ariane Khaledi, Susanne Häussler, James C. Paulson, Anne Imberty and Alexander Titz. Chem. Sci., 2016, Advance Article, DOI: 10.1039/C6SC00696E