Bacterial cell-to-cell communication facilitates coordinated expression of specific genes in a growth rate-II and cell density-dependent manner, a process known as quorum sensing. While the discovery of a diffusible Escherichia coli signaling pheromone, termed autoinducer 2 (AI-2), has been made along with several quorum sensing genes, the overall number and coordination of genes controlled by quorum sensing through the AI-2 signal has not been studied systematically. We investigated global changes in mRNA abundance elicited by the AI-2 signaling molecule through the use of a luxS mutant that was unable to synthesize AI-2. Remarkably, 242 genes, comprising ca. 5.6% of the E. coli genome, exhibited significant transcriptional changes (either induction or repression) in response to a 300-fold AI-2 signaling differential, with many of the identified genes displaying high induction levels (more than fivefold). Significant induction of ygeV, a putative 54 -dependent transcriptional activator, and yhbH, a 54 modulating protein, suggests 54 may be involved in E. coli quorum sensing.Many bacteria have evolved the ability to condition culture medium by secreting low-molecular-weight signaling pheromones in association with growth phase to control expression of specific genes, a process termed quorum sensing (19). Physiological processes controlled by quorum sensing occur in diverse species of bacteria and include bioluminescence (17), antibiotic biosynthesis (4), pathogenicity (34), and plasmid conjugal transfer (18). While acyl-homoserine lactones (HSL) appear to be the predominant quorum signal (or autoinducer [AI]) used by host-associated gram-negative bacteria, discovery of a second signaling pathway in the marine bacterium Vibrio harveyi (6,8,41) revealed an alternate AI, termed AI-2, which regulates bioluminescence in conjunction with AI-1 (N-(3-hydroxybutanoyl)-L-homoserine lactone) (7).Importantly, AI-2 (or AI-2-like) activity has been observed in virtually all strains of pathogenic and nonpathogenic Escherichia coli and Salmonella enterica serovar Typhimurium (16,(40)(41)(42), requiring the luxS gene for synthesis (43). The physiological role of AI-2 in E. coli has not been clearly elucidated, but initial findings indicate that inhibition of chromosomal replication was subject to a quorum sensing mechanism (52). More recently, quorum sensing in E. coli has been implicated in regulating the expression and activity of SdiA, a LuxR-type transcriptional activator of the cell division genes ftsQAZ, through AI-2 (15, 39). In addition, extracellular factors which accumulate in enterohemorrhagic E. coli O157:H7 culture supernatants bind to the N-terminal region of SdiA for controlling the expression of virulence factors in a quorum-dependent fashion (25). Besides possible roles in cell division and pathogenesis, quorum sensing in E. coli was postulated to play a role in stationary phase gene expression (23, 27, 39), perhaps in a bimodal fashion with the stationary phase sigma factor rpoS or with other yet-to-be-determin...

Cell polarity is critical for the form and function of many cell types. During polarity establishment, cells define a cortical “front” that behaves differently from the rest of the cortex. The front accumulates high levels of the active form of a polarity-determining Rho-family GTPase (Cdc42, Rac, or Rop), which then orients cytoskeletal elements through various effectors to generate the polarized morphology appropriate to the particular cell type [1, 2]. GTPase accumulation is thought to involve positive feedback, such that active GTPase promotes further delivery and/or activation of more GTPase in its vicinity [3]. Recent studies suggest that once a front forms, the concentration of polarity factors at the front can increase and decrease periodically, first clustering the factors at the cortex and then dispersing them back to the cytoplasm [4–7]. Such oscillatory behavior implies the presence of negative feedback in the polarity circuit [8], but the mechanism of negative feedback was not known. Here we show that, in the budding yeast Saccharomyces cerevisiae, the catalytic activity of the Cdc42-directed GEF is inhibited by Cdc42-stimulated effector kinases, thus providing negative feedback. We further show that replacing the GEF with a phosphosite-mutant GEF abolishes oscillations and leads to the accumulation of excess GTP-Cdc42 and other polarity factors at the front. These findings reveal a mechanism for negative feedback and suggest that the function of negative feedback via GEF inhibition is to buffer the level of Cdc42 at the polarity site.

Summary Cortical domains are often specified by the local accumulation of active GTPases. Such domains can arise through spontaneous symmetry breaking, suggesting that GTPase accumulation occurs via positive feedback. Here, we focus on recent advances in fungal and plant cell models, where new work suggests that polarity-controlling GTPases develop only one “front” because GTPase clusters engage in a winner-takes-all competition. However, in some circumstances two or more GTPase domains can co-exist, and the basis for the switch from competition to coexistence remains an open question. Polarity GTPases can undergo oscillatory clustering and dispersal, suggesting that these systems contain negative feedback. Negative feedback may prevent polarity clusters from spreading too far, regulate the balance between competition and co-existence, and provide directional flexibility for cells tracking gradients.