Structural Biology of Bacillus subtilis Biofilms

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Microorganisms form surface-attached communities, termed biofilms, which promote a synergistic lifestyle where an extracellular matrix (ECM) provides protection against environmental stress, including host immune reactions or antibiotic treatment. Evidently, their occurrence may produce health complications, for example in connection with implants or on teeth. The principles according to which the ECM is formed are important to understand, especially as its components do not only serve structural functions but can also be involved in signalling processes. An improved knowledge on the structure and function of the ECM could allow the development of new and better tailored antibacterial treatments, particularly those directed against biofilm forming (antibiotic-resistant) pathogens. Yet, there is a lack of methodological approaches for investigating the in vivo situation on the molecular level. Recent developments in solid-state NMR, electron microscopy and imaging by mass spectrometry promise access to unprecedented views into the ECM and in particular into the distribution of individual components and their interactions. Here, biofilms of the gram-positive organism B. subtilis serve as a model system. They are attractive targets, since a number of mechanistic studies are available that fuel follow-up investigations. As a start, we determine the in-vivo structure of TasA fibrils, investigate their interactions with TapA and EPS in vitro and in biofilms by biophysical techniques and structural methods, and study overall biofilm composition. The long-term goal of this project is a comprehensive, sufficiently resolved representation of biofilm structure at various scales. A long-term aim is the detection of gradients of large or small components over an entire biofilm or within the ECM. The results are relevant for understanding B.anthracis and B.aureus survival and infectivity.