The DNA Regulator Lrp is involved with the Pseudomonas quinolone signal (PQS) quorum sensing network
Disciplines
Microbial Physiology
Abstract (300 words maximum)
The opportunistic human pathogen Pseudomonas aeruginosa controls the transcription of multiple virulence genes through a coordinated quorum sensing network hierarchy. Pseudomonas Quinolone Signal (PQS), which has been identified as 2-heptyl-3-hydroxy-4-quinolone, is the third quorum sensing system, with the other two being the acyl homoserine lactones of las and rhl. Phenotypic analysis of an Lrp insertion mutant, PW9942, suggests that Lrp is involved in biofilm production and siderophore production, which have also been shown to be regulated in part by PQS. We investigated the molecular interaction between the Lrp DNA binding protein and the pqsA-E biosynthetic operon. pqsA-E is transcribed as a single operon with one upstream control region. Using Biolayer Interferometry, we demonstrate here that Lrp recognizes and binds to the PQS regulatory region and may play a role in the regulation of the quorum sensing pathway. This interaction with the quorum sensing network represents a novel function of Lrp not previously reported. This also supports our previous studies suggesting Lrp has a global regulatory role (albeit indirectly) in P. aeruginosa perhaps by influencing the PQS signaling factor in the intercellular signaling network of quorum sensing. Although it is known that PQS regulates the production of virulence factors, understanding the complete role and interactions between Lrp and PQS within the quorum sensing network may lead to new targets for the development and therapeutic applications for treatment against hospital-acquired infections.
Academic department under which the project should be listed
CSM - Molecular and Cellular Biology
Primary Investigator (PI) Name
Melanie C. Griffin
The DNA Regulator Lrp is involved with the Pseudomonas quinolone signal (PQS) quorum sensing network
The opportunistic human pathogen Pseudomonas aeruginosa controls the transcription of multiple virulence genes through a coordinated quorum sensing network hierarchy. Pseudomonas Quinolone Signal (PQS), which has been identified as 2-heptyl-3-hydroxy-4-quinolone, is the third quorum sensing system, with the other two being the acyl homoserine lactones of las and rhl. Phenotypic analysis of an Lrp insertion mutant, PW9942, suggests that Lrp is involved in biofilm production and siderophore production, which have also been shown to be regulated in part by PQS. We investigated the molecular interaction between the Lrp DNA binding protein and the pqsA-E biosynthetic operon. pqsA-E is transcribed as a single operon with one upstream control region. Using Biolayer Interferometry, we demonstrate here that Lrp recognizes and binds to the PQS regulatory region and may play a role in the regulation of the quorum sensing pathway. This interaction with the quorum sensing network represents a novel function of Lrp not previously reported. This also supports our previous studies suggesting Lrp has a global regulatory role (albeit indirectly) in P. aeruginosa perhaps by influencing the PQS signaling factor in the intercellular signaling network of quorum sensing. Although it is known that PQS regulates the production of virulence factors, understanding the complete role and interactions between Lrp and PQS within the quorum sensing network may lead to new targets for the development and therapeutic applications for treatment against hospital-acquired infections.