Quorum-Sensing Regulation of a Copper Toxicity System in Pseudomonas aeruginosa

Abstract

The LasR/LasI quorum-sensing system in Pseudomonas aeruginosa influences global gene expression and mediates pathogenesis. In this study, we show that the quorum-sensing system activates, via the transcriptional regulator PA4778 , a copper resistance system composed of 11 genes. The quorum-sensing global regulator LasR was recently shown to directly activate transcription of PA4778 , a cueR homolog and a MerR-type transcriptional regulator. Using molecular genetic methods and bioinformatics, we verify the interaction of LasR with the PA4778 promoter and further demonstrate the LasR binding site. We also identify a putative PA4778 binding motif and show that the protein directly binds to and activates five promoters controlling the expression of 11 genes— PA3519 to - 15 , PA3520 , mexPQ-opmE , PA3574.1 , and cueA , a virulence factor in a murine model. Using gene disruptions, we show that PA4778 , along with 7 of 11 gene targets of PA4778, increases the sensitivity of P. aeruginosa to elevated copper concentrations. This work identifies a cellular function for PA4778 and four other previously unannotated genes ( PA3515 , PA3516 , PA3517 , and PA3518 ) and suggests a potential role for copper in the quorum response. We propose to name PA4778 cueR .