Pseudomonas aeruginosa LasR overexpression leads to a RsaL-independent pyocyanin production inhibition in a low phosphate condition.

Several Pseudomonas aeruginosa virulence-related traits like pyocyanin are regulated by an intricate regulatory network called quorum sensing (QS) that relies on transcriptional regulators that are activated through binding to a self-produced molecule called an autoinducer (AI). QS is composed of three systems, Las, Rhl and Pqs. In the Las system, the regulatory protein LasR interacts with its AI to activate the other two QS systems. In turn, the Rhl and Pqs systems regulate the expression of multiple virulence-related genes, such as the genes of the reiterated operons phzA1B1C1D1E1F1G1 and phzA2B2C2D2E2F2G2 involved in pyocyanin production. The Las system also regulates the negative regulator RsaL, which provides negative feedback to the QS-response, including repression of pyocyanin synthesis genes. In this work, we describe that LasR can act as a negative regulator of phzA1 transcription and hence of pyocyanin production and that this regulation is independent of RsaL activity. This work contributes to the understanding of QS-dependent pyocyanin production and demonstrates a previously uncharacterized role of LasR as a repressor.