RT Journal Article SR Electronic T1 Bacterial c-di-GMP plays a key role in the evolution of host-association JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.03.20.533436 DO 10.1101/2023.03.20.533436 A1 Nancy Obeng A1 Anna Czerwinski A1 Daniel Schütz A1 Jan Michels A1 Jan Leipert A1 Florence Bansept A1 Thekla Schultheiß A1 Melinda Kemlein A1 Janina Fuß A1 Andreas Tholey A1 Arne Traulsen A1 Hinrich Schulenburg YR 2023 UL http://biorxiv.org/content/early/2023/03/20/2023.03.20.533436.abstract AB 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.