Swimming or sessile: the interplay between c-di-GMP signalling and flagellar motility

Bacteria have evolved multiple strategies to thrive in diverse environments. These include the ability to make rapid transitions between motile and sessile lifestyles, either of which might be favoured dependent of the environmental conditions. The central regulator for these lifestyle transitions is the second messenger cyclic dimeric guanosine monophosphate (c-di-GMP), which in general, inhibits flagellar motility and promotes the formation of sessile biofilm communities. Reciprocally, flagellated cells suppress c-di-GMP synthesis or activate its degradation to preserve motility. The interplay between c-di-GMP signalling and motility occurs at multiple levels of regulation, with evolutionarily conserved general principles but species-specific molecular mechanisms enabling environmental adaptations. Recent studies, described in this review, have revealed the emergent complexity of the intricate cross-regulation between c-di-GMP signalling and flagellar motility, highlighting context-specific deviations from simple antagonism and underscoring the importance of studying transient dynamics of c-di-GMP, gene expression, and motility changes during the lifestyle transitions.