Fighting antimicrobial resistant infections by high-throughput discovery of biofilm-disrupting agents and mechanisms
Therapeutics
- Morten Kjos, Norwegian University of Life Sciences, Norway (Coordinator)
- Jan-Willem Veening, University of Lausanne, Switzerland (Partner)
- Athanasios Typas, European Molecular Biology Laboratory, Germany (Partner)
- Christoph Merten, European Molecular Biology Laboratory, Germany (Partner)
Antimicrobial resistance is a growing problem worldwide. Many bacterial infections are nowadays often difficult to treat due to increasing antimicrobial resistance. Infections are particularly problematic if they are associated with biofilms. Biofilms are structured communities of bacteria, which are attached to surfaces. Infections typically caused by biofilms are wound-infections and urinary tract infections. The surface-attached biofilms are held together by a slimy matrix of polysaccharides, lipids, DNA and proteins. The matrix protects the bacterial cells against antibiotics and adds to the already existing resistance, making the infection treatment highly problematic. Novel strategies to treat such infections are therefore critical. In our project we focus on four bacteria which has been listed as high-priority pathogens by WHO. These are (1) uropathogenic E. coli (the major cause of urinary tract infections and catheher infections), (2) Pseudomonas aeruginosa (whose biofilms are associated with chronic infections in wounds or during cystic fibrosis), (3) Staphylococcus aureus (causing biofilm-associated chronic wound - and medical implant infections), and (4) Streptococcus pneumoniae (whose biofilms have been associated with middle-ear infections and pneumoniae). The DISRUPT project aims to identify new strategies to treat biofilm-associated infections. By inhibiting bacterial biofilms, the chances of infections will be reduced, and this will also resensitize the bacteria to existing antibiotics. To do this, we are using state-of-the-art genetic technologies (transposon sequencing, CRISPR interference) combined with high-throughput screens (screen for chemicals and microfluidic antibody screens) to identify anti-biofilm agents and mechanisms. The methods and resources we develop will be available for researchers worldwide, and will positively impact a range of research project related to AMR pathogens.
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