Influence by Molecules. A cell density threshold is required for the differentiation of swarmer cells to occur. However, quorum sensing has not been shown to be involved (246) so cell-to-cell communication may occur through alternative pathways. Putrescine triggers differentiation once an appropriate cell density is reached. This molecule is continuously produced and accumulates during growth of P. mirabilis via a biosynthetic pathway comprised of SpeA and SpeB. SpeA converts L-arginine to agmatine; in turn SpeB converts agmatine to putrescine. Putrescine is a component of the LPS core subunit in some strains of P. mirabilis (275). Mutants in speA or speB experience a severe delay in the onset of differentiation. This defect can be restored by the addition of exogenous putrescine (22) or ornithine (23), which is converted to putrescine via an alternative SpeF-mediated pathway. Uptake of putrescine by the PlaP putrescine importer is also necessary for normal swarming, and plaP speA double mutants cannot swarm in the presence of extracellular putrescine (254). Moreover, speB is upregulated in consolidation compared to swarming cells (65). Perhaps once cell density reaches a threshold during consolidation phase and enough putrescine has accumulated, it acts as a signal for cells to begin another period of migration. Overall, these studies suggest putrescine acts as an important cell-to-cell signaling molecule essential for differentiation. Exogenous histidine promotes swarming under non-permissive conditions which is dependent on intact putrescine and glutamine biosynthetic pathways. A mutant in the histidine biosynthetic pathway hisG experienced a delay in the onset of differentiation and subsequently swarming. The swarming defect of this mutant could be rescued by the addition of extracellular histidine (23). The role of histidine in swarming motility may be connected to the Leucine-responsive regulatory protein (Lrp), a bacterial nucleoid associated protein (NAP) and global transcriptional regulator. Lrp responds to the abundance of amino acids in the environment (27), including histidine, and Lrp is required for swarmer cell differentiation (24). Thus, histidine trigger differentiation through its interaction with Lrp.
