Movement over and colonization of surfaces are important survival strategies for bacteria, and many find it advantageous to perform these activities as a group, using quorum sensing to sample population size and synchronize behavior. It is puzzling however, that swarming-proficient and virulent strains of Vibrio parahaemolyticus are silenced for the vibrio archetypal pathway of quorum sensing. Here we describe the S-signal, a pheromone that can be communicated between cells in coculture to regulate surface colonization. This signal was harvested in cell-free supernatants and demonstrated to stimulate swarming gene expression at low cell density. The S-signal was generated by the pyridoxal phosphate-dependent aminotransferase ScrA; signal reception required the periplasmic binding protein ScrB and the membranebound GGDEF-EAL domain-containing protein ScrC. ScrC is a bifunctional enzyme that has the ability to form and degrade the second messenger bis-(3′-5′) cyclic dimeric GMP (c-di-GMP). ScrA in neighboring cells was able to alter the activity of ScrC in a ScrB-dependent manner, transforming ScrC's repressing ability to inducing activity with respect to swarming. Conversely, cell-cell signaling repressed capsule gene expression. In summary, we report that quorum sensing can stimulate swarming in V. parahaemolyticus; it does so via an alternative pathway capable of generating an autoinducing signal that influences c-di-GMP, thereby expanding the lexicon and language of cell-cell communication. These signals are diverse and include linear and cyclic peptides, long-and short-chain N-acyl-homoserine lactones, γ-quinolones, and unsaturated fatty acids (reviewed in refs. 1 and 2). Some of these signals are easily diffusible small molecules, whereas others are more hydrophobic and can be membrane-or vesicle-associated (3). Many of these communication signals are highly genus or species specific, although one, the furanosyl borate diester product of LuxS, seems a more universally synthesized and recognized molecule (reviewed in ref. 4). These molecules are collectively called "autoinducers." It is thought that bacteria produce and use such signaling molecules to detect not only their neighbors and cell-population density, but also as a gauge to sample aspects of their environment, such as diffusion and confinement (reviewed in refs. 5 and 6). In a broad sense, quorum sensing allows coordination of population-wide activities, including swarming motility on surfaces, bioluminescence, virulence factor production, and biofilm dynamics (reviewed in refs. 7-9).In this context, the personality of Vibrio parahaemolyticus is perplexing because this bacterium clearly participates in behaviors that are social in nature: it is an excellent swarmer, a robust biofilm former, and a pathogen (reviewed in ref. 10). However, many of these group activities occur in a seemingly asocial cell type (11,12). Specifically, V. parahaemolyticus displays On/Off phase switching with respect to the archetypal pathway of quorum sensing in the Vibrion...