Biofilm formation mechanisms – University of Copenhagen

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Biofilm formation mechanisms

Biofilms are communities of aggregated bacterial cells embedded in a self-produced extracellular polymeric matrix, and they are associated with numerous chronic infections as bacteria in biofilms are tolerant to antimicrobial treatments and host defences and thus are very difficult, and in some cases impossible, to eradicate.

Knowledge of the factors involved in biofilm formation and maintenance is important to develop measures to prevent biofilm formation or to remove existing biofilms. Biofilm formation occurs in a sequence of distinct events, including initial cell-to-surface or cell-to-cell attachment, microcolony formation, biofilm maturation, and biofilm dispersal.

The ability of bacteria to produce extracellular matrix components that enable them to stick to surfaces and to each other 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 and DNA.

Although the elements used for adhesion and biofilm formation varies amongst bacterial species, it appears that there are common underlying features. Recent research suggests that the molecule cyclic diguanosine monophosphate (c-di-GMP) may constitute a ubiquitous intracellular regulator of bacterial biofilm formation. The level of c-di-GMP in the bacteria is determined by diguanylate cyclases and phosphodiesterases which contain characteristic GGDEF and EAL protein domains as well as regulatory domains. While the available evidence suggest that the second messenger c-di-GMP regulates the production of exopolysaccharide and exoprotein matrix components, the production of extracellular DNA appears to be governed by autolysins or pro-oxidants that are produced by the bacteria and mediate lysis of a subpopulation of them.

Proper characterization of the regulation of GGDEF and EAL domain proteins, identification of the effector molecules and target processes that are affected by c-di-GMP, and elucidation of the mechanisms of DNA-release, will improve our understanding of the biofilm mode of growth and the transition between planktonic and biofilm lifestyles. This knowledge will enable us to identify targets for new drugs that can prevent or cure biofilm infections.

Projects focussed on these issues are currently funded by the Danish Council for Independent Research, the Lundbeck foundation, and by Sofus Carl Emil Friis og hustru Olga Doris Friis’ Legat.

Contact person:

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