The opportunistic pathogenic bacterium Pseudomonas aeruginosa uses quorum-sensing signaling systems as global regulators of virulence genes. There are two quorum-sensing signal receptor and signal generator pairs, LasR-LasI and RhlR-RhlI. The recently completed P. aeruginosa genome-sequencing project revealed a gene coding for a homolog of the signal receptors, LasR and RhlR. Here we describe a role for this gene, which we call qscR. The qscR gene product governs the timing of quorum-sensing-controlled gene expression and it dampens virulence in an insect model. We present evidence that suggests the primary role of QscR is repression of lasI. A qscR mutant produces the LasI-generated signal prematurely, and this results in premature transcription of a number of quorum-sensing-regulated genes. When fed to Drosophila melanogaster, the qscR mutant kills the animals more rapidly than the parental P. aeruginosa. The repression of lasI by QscR could serve to ensure that quorum-sensing-controlled genes are not activated in environments where they are not useful.
The opportunistic pathogen Pseudomonas aeruginosa uses a cell-cell communication system termed "quorum sensing" to control production of public goods, extracellular products that can be used by any community member. Not all individuals respond to quorum-sensing signals and synthesize public goods. Such social cheaters enjoy the benefits of the products secreted by cooperators. There are some P. aeruginosa cellular enzymes controlled by quorum sensing, and we show that quorum sensing-controlled expression of such private goods can put a metabolic constraint on social cheating and prevent a tragedy of the commons. Metabolic constraint of social cheating provides an explanation for private-goods regulation by a cooperative system and has general implications for population biology, infection control, and stabilization of quorum-sensing circuits in synthetic biology.Acyl-homoserine lactone (AHL) quorum sensing is common among Proteobacteria. This is a form of cell-cell communication that allows bacteria to monitor their population density and activate specific sets of genes when populations have reached a threshold density (1-3). Quorum sensing controls the production of a variety of public goods, functions shared by all individuals in the group. Experiments with P. aeruginosa support the view that quorum sensing controls cooperativity between P. aeruginosa cells (4-6). AHL signaling in P. aeruginosa is complex and involves multiple signals and receptors (7). A key system involves LasI, which generates the diffusible AHL signal N-3-oxododecanoylhomoserine lactone (C12-HSL) and LasR, a C12-HSL-responsive transcription activator (8). Together C12-HSL and LasR directly activate dozens of genes (9), with a heavy overrepresentation of genes coding for extracellular factors or production of extracellular factors, although there are some LasR-activated genes coding for cellular enzymes. Cellular enzymes are not shared among individuals so we call them private goods (10). By contrast, LasR-activated extracellular proteases are known as public goods (5). Growth of P. aeruginosa with casein or bovine serum albumin as the sole source of carbon and energy requires these proteases and encourages the emergence of LasR-mutant social cheaters (4, 5), which do not incur the cost of expressing quorum-controlled functions but benefit from the public goods produced by other members of the group. These cheaters have the potential to cause a "tragedy of the
We report the cloning and determination of the nucleotide sequence of the gene encoding nucleoside diphosphate kinase (Ndk) from Pseudomonas aeruginosa. The amino acid sequence of Ndk was highly homologous with other known bacterial and eukaryotic Ndks (39.9 to 58.3% amino acid identity). We have previously reported that P. aeruginosa strains with mutations in the genes algR2 and algR2 algH produce extremely low levels of Ndk and, as a consequence, are defective in their ability to grow in the presence of Tween 20, a detergent that inhibits a kinase which can substitute for Ndk. Hyperexpression of ndk from the clone pGWS95 in trans in the P. aeruginosa algR2 and algR2 algH double mutant restored Ndk production to levels which equalled or exceeded wild-type levels and enabled these strains to grow in the presence of Tween 20. Hyperexpression of ndk from pGWS95 in the P. aeruginosa algR2 mutant also restored alginate production to levels that were approximately 60% of wild type. Nucleoside diphosphate kinase activity was present in both the cytosolic and membrane-associated fractions of P. aeruginosa. The cytosolic Ndk was non-specific in its transfer activity of the terminal phosphate from ATP to other nucleoside diphosphates. However, the membrane form of Ndk was more active in the transfer of the terminal phosphate from ATP to GDP resulting in the predominant formation of GTP. We report in this work that pyruvate kinase and Ndk form a complex which alters the specificity of Ndk substantially to GTP. The significance of GTP in signal transduction events within the cell and in the production of GDP-mannose, an essential alginate precursor, clearly indicates the importance of Ndk in cellular processes as well as in alginate synthesis.
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