Project Details
Projekt
How do biofilms heal their wounds?
Subject Area
Metabolism, Biochemistry and Genetics of Microorganisms
Biophysics
Biophysics
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 504222949
Bacterial biofilms are heterogeneous assemblies of bacterial cells embedded in and held together by a self-secreted extracellular matrix (ECM). Once the biofilm is formed it is very hard to eradicate mechanically or biochemically. As a result, biofilms formed by pathogenic bacteria pose a significant challenge in medical contexts. This evidenced, for example, by the estimate that 80% of chronic bacterial infections involve biofilms such as in myocarditis or urinary tract infections. Biofilms are heterogeneous on multiple scales, genetically, phenotypically, structurally, and mechanically with complex cell-cell and cell-environment interactions. Increasingly often the analogy between biofilms and eukaryotic tissues is drawn; in the context of biofilms colonizing a host, biofilms are even suggested to be treated as a part of host tissues. One so far unanswered question that is pertinent to both contexts of tissue analogy and removal of unwanted biofilms is how biofilms are able to recover from a macroscopic damage. In this project, we use Bacillus subtilis, a powerful model system for biofilm formation studies. Combining microbiological and biophysical tools with theoretical modeling we aim to elucidate what is the natural response of the biofilm to a damage. To date, we have accumulated evidence on dynamical processes involved in wound healing, particularly highlighting the roles of residual cells and nutrient gradients in wound closure. However, we are still lacking understanding of how the sequence of events during recovery with respect to phenotypic, molecular, structural and mechanical levels unfolds and how those are interrelated. On the molecular and cellular levels, we will investigate how molecular signals drive cell phenotypic switches during biofilm growth from ECM production to sporulation thus creating spatio-temporal profile of the wound healing. On the macroscopic level of whole biofilms, we aim to quantify how the "scar" biofilm tissue differs from the “normally” developing biofilms at the level of their mechanical properties, water and metal ion content, and morphology and how those are determined by the underlying molecular and cell-phenotypic signatures. Our project combines modern structural, cell sorting, mass spectrometry, mechanobiology and biochemistry approaches together with advanced theoretical modeling. Results of this work will not only provide us with quantitative understanding of how bacterial biofilms cope with damage but will also shed light on multiple aspects of their natural development from a comprehensive multi-scale and interdisciplinary perspective.
DFG Programme
Priority Programmes
International Connection
Israel
