Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.184 (LasR)
 897 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Pseudomonas aeruginosa, N-acylhomoserine lactone signals regulate the expression of several hundreds of genes, via the transcriptional regulator LasR and, in part, also via the subordinate regulator RhlR. This regulatory network termed quorum sensing contributes to the virulence of P. aeruginosa as a pathogen. The fact that two supposed PAO1 wild-type strains from strain collections were found to be defective for LasR function because of independent point mutations in the lasR gene led to the hypothesis that loss of quorum sensing might confer a selective advantage on P. aeruginosa under certain environmental conditions. A convenient plate assay for LasR function was devised, based on the observation that lasR mutants did not grow on adenosine as the sole carbon source because a key degradative enzyme, nucleoside hydrolase (Nuh), is positively controlled by LasR. The wild-type PAO1 and lasR mutants showed similar growth rates when incubated in nutrient yeast broth at pH 6.8 and 37 degrees C with good aeration. However, after termination of growth during 30 to 54 h of incubation, when the pH rose to > or = 9, the lasR mutants were significantly more resistant to cell lysis and death than was the wild type. As a consequence, the lasR mutant-to-wild-type ratio increased about 10-fold in mixed cultures incubated for 54 h. In a PAO1 culture, five consecutive cycles of 48 h of incubation sufficed to enrich for about 10% of spontaneous mutants with a Nuh(-) phenotype, and five of these mutants, which were functionally complemented by lasR(+), had mutations in lasR. The observation that, in buffered nutrient yeast broth, the wild type and lasR mutants exhibited similar low tendencies to undergo cell lysis and death suggests that alkaline stress may be a critical factor providing a selective survival advantage to lasR mutants.
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PMID:Quorum-sensing-negative (lasR) mutants of Pseudomonas aeruginosa avoid cell lysis and death. 1599 2

Pseudomonas aeruginosa quorum sensing (QS) regulates expression of dozens of genes in a cell density-dependent manner. Many QS-regulated genes code for production of extracellular factors, "public goods" that can benefit the entire population. This cooperation encourages individuals to cheat by using but not producing public goods. QS also controls expression of a limited number of genes encoding "private" cellular enzymes like Nuh, an enzyme involved in adenosine catabolism. Growth of P. aeruginosa on casein requires QS-regulated production of an extracellular protease and is an example of cooperative behavior. When P. aeruginosa is transferred daily on casein, QS mutants emerge. These cheaters have mutations in lasR, which encodes the primary QS transcription factor. When growth is on casein and adenosine, cheater emergence is constrained. Here, we report the dynamics of LasR mutant invasion during growth on casein or casein plus adenosine. We show that LasR mutants have the greatest advantage during early to mid-logarithmic growth on casein. Addition of adenosine to casein medium constrains cheaters throughout growth. Our data support the view that co-regulation of the public protease and the private nucleosidase by QS stabilizes cooperation, and the data are not consistent with other proposed alternate hypotheses.
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PMID:Dynamics of cheater invasion in a cooperating population of Pseudomonas aeruginosa. 3130 1