Evolution and plasticity of cyclic di-nucleotide signaling networks in Bacteria

Nucleotides and in particular cyclic di-nucleotides frequently are mediators to transduce external and intrinsic signals. Cyclic di-GMP is a ubiquitous second messenger that regulates fundamental conserved behavioral changes in Bacteria.

In this project, we will in particular focus on the signal transduction within the cyclic di-GMP network by systematically mapping protein-protein interactions of cyclic di-GMP turnover proteins.

Furthermore, we will investigate the role of variability of cyclic di-GMP signaling components observed on the short and long term phylogenetic time scale in order to understand the mechanisms of conservation versus variability of components.

In this context, a single amino acid substitution in a cyclic di-nucleotide receptor led to a substantial alteration in functionality with promiscuous promotion of cell filamentation, downregulation of flagellar-based motility and alteration of agar-plate based rdar biofilm formation equally as affecting antimicrobial resistance.

Founded in microbial, molecular biology, system biology and biochemical approaches, following up on these fundamental, but poorly investigated questions of second messenger network functionality, conservation and variability will unravel novel principles of this ubiquitous second messenger signaling system and protein evolution, which will also eventually identify novel targets to combat intrinsic antimicrobial tolerance in biofilms.