Legionella quorum sensing meets cyclic-di-GMP signaling

[Display omitted] •L. pneumophila small molecule signaling comprises the quorum sensing autoinducer LAI-1 and c-di-GMP.•Legionella quorum sensing and c-di-GMP signaling regulate motility, virulence, natural competence and biofilm architecture.•The pleiotropic transcription factor LvbR links the Lqs system and c-di-GMP signaling.•Nitric oxide exogenously controls the Legionella c-di-GMP regulatory network. Bacterial gene regulation occurs through complex networks, wherein linear systems respond to intracellular or extracellular cues and engage on vivid crosstalk. The ubiquitous water-borne bacterium Legionella pneumophila colonizes various distinct environmental niches ranging from biofilms to protozoa, and – as an ‘accidental’ pathogen – the human lung. Consequently, L. pneumophila gene regulation evolved to integrate a broad spectrum of different endogenous and exogenous signals. Endogenous signals produced and detected by L. pneumophila comprise the quorum sensing autoinducer LAI-1 (3-hydroxypentadecane-4-one) and c-di-GMP. As an exogenous cue, nitric oxide controls the c-di-GMP regulatory network of L. pneumophila. The Legionella quorum sensing (Lqs) system regulates virulence, motility and natural competence of L. pneumophila. The Lqs system is linked to c-di-GMP signaling through the pleiotropic transcription factor LvbR, which also regulates the architecture of L. pneumophila biofilms. In this review, we highlight recent insights into the crosstalk of Legionella quorum sensing and c-di-GMP signaling.