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

In Pseudomonas aeruginosa, virulence determinants and biofilm formation are coordinated via a hierarchical quorum sensing cascade, which involves the transcriptional regulators LasR and RhlR and their cognate homoserine lactone activators C12-HSL [N-(3-oxododecanoyl)-L-homoserine lactone] and c4-hsl (n-butanoyl-L-homoserine lactone), which are produced by LasI and RhlI, respectively. The exoenzyme S regulon of P. aeruginosa, comprises genes for a type III secretion system and for four anti-host effector proteins (ExoS, T, U and Y), which are translocated into host cells. It is a reasonable assumption that this ExoS regulon should be downregulated in the biofilm growth state and thus should also be under the regulatory control of the Las/Rhl system. Therefore, an exoS'-gfp reporter construct was used, and the influence of the Las and Rhl quorum sensing systems and the effect of the stationary-phase sigma factor RpoS on regulation of the exoS gene was examined. Evidence is provided for downregulation of exoS during biofilm formation of P. aeruginosa PAO1. The rhlI mutant PDO100 and rhlR mutant PDO111, but not the lasI mutant PDO-JP1, showed approximately twofold upregulation of the exoS'-gfp reporter in comparison to PAO1. Upregulation of exoS'-gfp in the PDO100 mutant could be repressed to normal level by adding C4-HSL autoinducer, indicating a negative regulatory effect of RhlR/C4-HSL on exoS expression. As RhlR/C4-HSL is also involved in regulation of RpoS, the P. aeruginosa rpoS mutant SS24 was examined and the exoS'-gfp reporter was found to be fivefold upregulated in comparison to PAO1. For the first time evidence is reported for a regulatory cascade linking RhlR/RhlI and RpoS with the expression of the anti-host effector ExoS, part of the exoenzyme S regulon. Moreover, these data suggest that the exoenzyme S regulon may be downregulated in P. aeruginosa biofilms.
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PMID:Expression of Pseudomonas aeruginosa exoS is controlled by quorum sensing and RpoS. 1507 94

Surface adhered bacterial colonies or biofilms are an important problem in medical and food industries. Bacteria use a chemical language to monitor their quorum and to express virulence factors, which eventually help them in colonization and manifestation of an infection. The LasR-LasI and RhlR-RhlI quorum-sensing (QS) systems of Pseudomonas aeruginosa control expression of virulence factors in a population density-dependent fashion. In this study we investigated the role of synthetic analogs to RhlR-RhlI system of P. aeruginosa strains (PAO-1; wild-type and mutants JP-1, PDO-100, and JP-2) responsible for production of acyl-homoserine lactones-2; butanol homoserine lactone (AHL-2; C(4)-HSL). We synthesized double (QS1207) and single (QS0108) sulfur analogs against (C(4)-HSL; AHL-2), an autoinducer of Pseudomonas QS system. Extensive biological investigation of these analogs suggested a growth promoting activity for these analogs in Pseudomonas controlling biofilm production and exo-protease secretion. We hypothesized that these thiolactone analogs could be potentially utilized as potent drug-delivery vehicles against biofilm-producing pathogens. As a proof of principle we conjugated the single sulfur analog QS0108 with the broad-spectrum antibiotic, ciprofloxacin (QS0108-Cip). The QS analog-antibiotic conjugate was significantly more effective at disrupting both the nascent and mature biofilms of P. aeruginosa than the free antibiotic.
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PMID:Design, synthesis, and a novel application of quorum-sensing agonists as potential drug-delivery vehicles. 2088 84