Biofilm formation mechanisms – University of Copenhagen

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Biofilm formation mechanisms

Biofilms are communities of aggregated bacterial cells embedded in an extracellular polymeric matrix, and they are associated with numerous chronic infections, as bacteria in biofilms are tolerant to antimicrobial treatments and host defenses and thus are very difficult or impossible to eradicate. The ability of bacteria to produce extracellular matrix components is a prerequisite for biofilm formation. As the biofilm matures the resident bacteria become embedded and protected in this self-produced extracellular matrix which is composed of polysaccharide, protein, DNA and lipids.

Recent research suggests that the molecule cyclic diguanosine monophosphate (c-di-GMP) constitutes a ubiquitous intracellular regulator of bacterial biofilm formation. High levels of c-di-GMP induce the formation of biofilm matrix products and biofilm formation, whereas low c-di-GMP levels down-regulate synthesis of biofilm matrix components and induce a planktonic bacterial lifestyle. The level of c-di-GMP in bacteria is determined by diguanylate cyclases (DGCs) and phosphodiesterases (PDEs) which contain characteristic GGDEF and EAL/HD-GYP domains as well as regulatory domains.

Student projects may focus on obtaining knowledge of the regulation of the activity of DGCs and PDEs, and identification of the processes that are affected by c-di-GMP in Pseudomonas aeruginosa or Burkholderia cenocepacia, which are important pathogenic bacteria. This will improve our understanding of the biofilm mode of growth and the transition between planktonic and biofilm lifestyles. Moreover, this knowledge will reveal molecular targets that will enable us to force bacteria out of the biofilm lifestyle and into the planktonic lifestyle where they are more susceptible to antibiotics and host immune responses. Thereby new drugs that can prevent or cure biofilm infections can be developed.

Contact person
Tim Tolker-Nielsen, e-mail: ttn@sund.ku.dk, Tel: +45 26 24 56 90