Project Details
Projekt
Spatial regulation of bacterial antiphage defense systems within biofilms
Subject Area
General Genetics and Functional Genome Biology
Metabolism, Biochemistry and Genetics of Microorganisms
Metabolism, Biochemistry and Genetics of Microorganisms
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 569011257
Bacterial communities organized in biofilms have unique immune properties, which increase their resistance against bacteriophage predation. For instance, the extracellular physical barriers of biofilms limit phage spread and, therefore, increase phage resistance. In addition, a vast diversity of bacterial antiphage defense systems able to protect their hosts against phage infection has recently been discovered. However, how defense systems are involved in phage resistance in the context of bacterial multicellularity is poorly understood. This is because the molecular mechanisms of defense systems have been studied primarily in liquid culture using heterologous expression. Here, we hypothesize that bacterial communities regulate the expression of native defense systems in a spatial manner and at the single-cell level. To investigate this regulation, we propose to leverage Pseudomonas aeruginosa biofilms as a model system alongside innovative spatial transcriptomics imaging. Using BiofilmEx, a new method developed in the first funding period, we will visualize and quantify transcripts in millions of sessile bacteria in 3D at single-cell resolution to analyze defense system expression in full-scale P. aeruginosa biofilms. We will then study how this regulation influences phage replication by tracking phage infection in mixed biofilms of susceptible and resistant bacteria. The proposed methodological developments of this project are timely and will enable cooperation with other projects in the consortium to explore phenotypic variation in bacterial multicellularity. Together, we expect to make a leap forward in our understanding of defense system regulation and function in bacterial communities as well as in the available methods for studying biofilms.
DFG Programme
Priority Programmes
