Quantifying the Link Between Architectural Integrity and Adaptive Potential in Developing Biofilms

• Applicant: Professor Dr. Oskar Hallatschek
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 503995533

A fascinating aspect of biofilms is their dynamic self-organization, which produces a rich set of morphological features, including pronounced internal cell ordering, strong surface attachment and, at larger scales, wrinkles, folds, and channels. The emerging architecture supports biofilm survival, endows them with resilience against physical stresses and contributes to antibiotic tolerance. The integrity and function of the biofilm architecture is, however, threatened by adaptive mutations arising during biofilm growth if they expand and displace the wild type. Mechanisms that buffer against such “cancerous” mutations would promote robust biofilm development. Indeed, recent simulations and colony studies suggest that mechanical interactions can help keep weak mutations at bay, thus promoting the integrity of the architecture. On the other hand, suppressing beneficial mutations to sweep should hamper the community to adapt, for instance, to the very stresses that architecture buffers against (antibiotics, physical stresses). We, therefore, hypothesize a tradeoff between the architectural integrity of a biofilm and its ability to quickly adapt to environmental challenges. We plan to test whether such a tradeoff exists and explore whether it is tipped towards integrity or adaptability, possibly depending on the mutations and their effect. V. cholerae is the perfect model system to explore the hypothesized tradeoff. Apart form its public health significance and genetic tractability, V. cholerae biofilms have a well-characterized morphogenesis, much of it studied at single-cell resolution. We can thus build on an excellent understanding of the wild type architecture of V. cholerae biofilms to explore how it is perturbed by or buffers against evolutionary processes. To this end, we employ advanced imaging technologies adapted to the 3D biofilm context and spontaneously mutating fluorescent reporter constructs to track mutant clones in space and time. These data will be used to develop a predictive biofilm model of natural selection and genetic drift, allowing us to test our hypothesis of an emergent tradeoff between adaptive potential and architectural integrity. Resolving the tradeoff between biofilm development and evolution will be an important step towards understanding eco-evolutionary feedbacks in single species biofilms. More generally, an improved understanding of the basic forces of evolution in biofilms will provide a baseline to model a wide range of evolutionary processes. We envision the newly developed synthetic mutagenesis system as well as the biofilm evolution model to be useful to numerous other SPP projects with interest in studying or accounting for evolutionary processes in biofilms.

• DFG Programme: Priority Programmes
• Subproject of: SPP 2389: Emergent Functions of Bacterial Multicellularity
• International Connection: Switzerland
• Cooperation Partner: Professor Dr. Knut Drescher, Ph.D.