%0 Journal Article %A Nancy Obeng %A Anna Czerwinski %A Daniel Schütz %A Jan Michels %A Jan Leipert %A Florence Bansept %A Thekla Schultheiß %A Melinda Kemlein %A Janina Fuß %A Andreas Tholey %A Arne Traulsen %A Hinrich Schulenburg %T Bacterial c-di-GMP plays a key role in the evolution of host-association %D 2023 %R 10.1101/2023.03.20.533436 %J bioRxiv %P 2023.03.20.533436 %X Most microbes evolve faster than their hosts and should therefore drive evolution of host-microbe interactions1–3. However, relatively little is known about the characteristics that define the adaptive path of microbes to host-association. In this study we have identified microbial traits that mediate adaptation to hosts by experimentally evolving the bacterium Pseudomonas lurida with the nematode Caenorhabditis elegans. We repeatedly observed the evolution of beneficial host-specialist bacteria with improved persistence in the nematode, achieved by mutations that uniformly upregulate the universal second messenger c-di-GMP. We subsequently upregulated c-di-GMP in different Pseudomonas species, consistently causing increased host-association. Comparison of Pseudomonad genomes from various environments revealed that c-di-GMP underlies adaptation to a variety of hosts, from plants to humans, suggesting that it is fundamental for establishing host-association.Competing Interest StatementThe authors have declared no competing interest. %U https://www.biorxiv.org/content/biorxiv/early/2023/03/20/2023.03.20.533436.full.pdf