SPM studies on single cellular interactions with biofilm

Many infectious diseases in humans are caused by virulent biofilms that result from complex interactions between specific microorganisms and their extracellular environments. Involved in biofilm formation are various types of filamentous structures that also form immunogenic complexes with environmental DNA. Although bacterial infections are known to contribute to pathogenesis by inducing cell death and inflammation, the exact mechanism and the molecular players that lead to cell binding and pathogenesis remain obscure to date. This project aims at exploring the unique physical, biochemical, and electrostatic properties of living bacterial cells and biofilms. Using a portfolio of scanning probe microscopy (SPM)-based methodologies with nano-metric spatial resolution and single molecule detection sensitivity, we will study the molecules involved in bacterial attachment to surfaces and biofilm development. Chemical, electrostatic, and mechanical properties of biofilms will be monitored during maturation. Among the infections caused by pathogenic bacteria is a broad range of autoimmune diseases, in which a persons immune system produces an inappropriate response against its own cells, tissues and organs, resulting in inflammation and damage. We will thus extend our studies to characterize the molecular interactions of biofilms with cells of the immune system and detect immune response triggered by biofilm binding. The overall aim of the project is to fundamentally extend our understanding of biofilm formation in relation to function and disease. PR_abstract_eng

The overall aim in this project was to understand the detailed molecular mechanisms underlying bacterial biofilm formation and development of pathogenicity. To this end, we expanded the understanding of the microbial structure at the nano-scale, ideally on the single molecular level, through all phases from initial attachment to biofilm formation to immune stimulation. We were also able to extend our approach to a broader range of pathogens, not only bacterial but also viral pathogenicity, as was the case during the last pandemic. Finally, the newly gained knowledge is important for the development of antibacterial drugs against pathogen-related disease and for the ultra-sensitive detection of pathogenicity. Many questions still remain to be answered about pathogens and their molecular roles in disease. In this project we developed molecular recognition tools to overcome the limitations of other methods in terms of sensitivity and resolution. Overall, we have obtained structural information of pathogens, and molecular details of biomolecules involved in pathogen-related disease mechanisms.