Title:
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Regulation of phenazine biosynthesis by quorum sensing in Pseudomonas aeruginosa : a systems biology
approach
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Pseudomonas aeruginosa has sophisticated mechanisms to adapt to environmental changes and control virulence factor production. The las, rhl and pqs quorum sensing systems play a central role in this adaptation. These three systems are interlinked and have an important role in the control of pyocyanin production. The biosynthesis of the pyocyanin precursor phenazine-1-carboxylic acid (PCA) is mediated by either of two nearly identical phzABCDEFG operons. Due to the high sequence conservation between these operons analysis of their individual expression levels by RNA hybridisation, qRT-PCR or transcriptomic analysis is challenging. Hence, to overcome this difficulty and gain a better understanding of the links between QS and phenazine production new dual reporter systems which can simultaneously measure the transcriptional levels of the phzAl -G1 and phzA2-G2 operons have been developed.
These reporter systems have revealed that all three QS systems play a role in activation of each phenazine operon and that each operon is differentially regulated by QS. A significant delay between the initiation of transcription of these two operons has been observed. Using a combination of computer modelling and transcriptional analysis of the phzAl-G1 and phzA2- G2 operons in a range of QS mutant's new links between QS and phenazine production have been revealed. A new model for the regulation of phenazine production by QS is presented which has provided some clues as to why two identical operons are stably maintained in
P. aeruginosa.
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