Characterization and Simulation of Biofilm Growth and Degradation (SIIRI - DFG TRR 298)

Microbial biofilms colonize implant surfaces and cause severe infections that are hard to eradicate. Thus, prevention of biofilm formation on implant surfaces and development of effective strategies to combat biofilms is essential to improve implant safety. Reproducing biofilm dynamics in laboratory is a complex task given the number of elements controlling development of implant-associated biofilms. Consequently, characterization of anti-biofilm drugs requires intricate methodologies, can be low-throughput and may fail to predict in vivo situation. Numerical simulation techniques can help to overcome the current methodological limitations and make evaluation of anti-biofilm strategies much more efficient. This project (B07) aims at stimulating development and drug-induced degradation of implant-associated biofilms, in order to select drugs for sensor/actor systems developed in the B01, B04, B05 and B06 subprojects of this CRC and guide adjustment of drug release systems. Complex physicochemical and electrostatic interactions between bacteria and implant surface as well as between different bacterial cells will be modelled at the nanoscale while biofilm itself will be defined on the microscale with a help of continuum mechanical description. Nano- and microscale effects will be coupled through homogenization processes. In silico experiments will generate predictions and hypothesis, e.g. regarding the role of drug transport, flow conditions, metabolic factors, or cell-cell interactions. To generate biofilm parameters and validate simulations, biofilms observed in patients will be closely reproduced using in vitro biofilm models formed by clinical isolates or culturomes, i.e. assemblages of co-isolated clinical strains. Importantly, this approach preserves clinically relevant genotypes, pheno-types and interspecies interactions. Structure, composition and transcriptional activity of biofilms will be studied yielding parameters for simulations. Drug-induced biofilm degradation will be characterized in a spatio-temporal manner to reveal best drug candidates and quantify drug transport. Parameters describing biofilms will be also obtained from the other CRC subprojects. Mutually supportive simulations and in vitro models will exchange parameters to adjust and validate biofilm predictions. Finally, simulations are applied to select anti-biofilm drugs for sensor/actor systems to be optimized together with other CRC members. Thus, the project addresses clinically relevant, fundamental, biophysical processes and will facilitate the development of im-plant designs tailored for effective biofilm prevention and control, which will in future contribute to a signifi-cant increase in implant safety.

Further information on B07.

Further information on TRR 298 (SIIRI).