Quorum Sensing

Reaching a Quorum Isn’t Simple

Science Signaling  01 Mar 2011:
Vol. 4, Issue 162, pp. ec63
DOI: 10.1126/scisignal.4162ec63

Bacterial quorum sensing regulates the transition from a solitary mode of existence to collective cell behaviors, such as biofilm formation, swarming, and virulence. In the marine bacterium Vibrio harveyi, high cell density induces bioluminescence, and quorum sensing is mediated by secreted signaling molecules called autoinducers (AIs), which bind to two-component cell surface receptors. At low cell density (LCD), AI concentration is low, and the unliganded receptors are active kinases that phosphorylate and activate LuxO, which, in turn, activates the expression of five qrr genes. The Qrrs are small noncoding RNAs (sRNAs) that repress translation of the master quorum-sensing regulator LuxR, the absence of which correlates with expression of genes characteristic of solitary bacteria. At high cell density (HCD) and high AI concentration, the liganded receptors act as phosphatases that deactivate LuxO, thus allowing production of LuxR and activation of genes associated with group behaviors. In addition to repressing LuxR translation, the Qrrs also repress the translation of LuxO, AI synthases, and AI receptors. There are multiple feedback mechanisms regulating Qrrs, including activation of the qrr genes by LuxR and by LuxO. Precise regulation of Qrr production is thus a key feature of the quorum-sensing mechanism. Rutherford et al. identified the winged-helix transcription factor AphA in a screen for transposon insertions that affected expression of qrr4 at LCD. AphA was most abundant at LCD and repressed expression of qrr2, qrr3, and qrr4 in vivo. AphA directly bound to the qrr4 promoter in vitro, making it likely that AphA directly repressed all three genes. AphA also directly repressed LuxR and its own expression. Moreover, LuxR directly repressed aphA, and Qrr4 activated AphA production through an unknown mechanism. These results indicate that AphA inhibits quorum sensing by repressing LuxR but also negatively feeds back on the pathway by inhibiting its own expression and that of the qrr genes. Microarray analysis revealed that AphA promoted the expression of 99 genes and repressed 197 genes at LCD; a subset of these genes received inputs from both AphA and LuxR. Studies in the related species Vibrio cholerae indicated that Qrrs also activated aphA to regulate quorum sensing in this human pathogen. The complex regulatory model that emerges is one in which Qrrs promote production of AphA and repress production of LuxR at LCD; when Qrr production ceases at HCD, LuxR is produced. AphA and LuxR reciprocally repress one another, and both feed back to inhibit and stimulate qrr expression, respectively. Multiple negative feedback mechanisms operate to fine-tune the amounts of Qrrs that are produced, and this precision is the key to proper regulation of quorum sensing. AphA and LuxR are thus opposing forces in the quorum-sensing pathway and jointly determine the characteristic LCD and HCD transcriptomes.

S. T. Rutherford, J. C. van Kessel, Y. Shao, B. L. Bassler, AphA and LuxR/HapR reciprocally control quorum sensing in vibrios. Genes Dev. 25, 397–408 (2011). [Abstract] [Full Text]