QS hierarchy. The LasI AHL synthase (blue arrow) produced the 3-oxo-C12-HSL (blue circle), which associated with the LasR LuxR regulator (in red arrow for lasR and red square for the LasR protein). LasR bound to 3-oxo-C12-HSL activates rhlR and rhlI (golden and beige arrows, respectively). RhlI produces C4-HSL (beige circle) and, after binding on the RhlR regulator (golden square), this system autoregulates itself. LasR bound to 3-oxo-C12-HSL activates the pqsABCDE operon (dark green arrows), as well as the phnAB genes (light green arrows). The product of these genes is HHQ (dark green circle), which is converted to PQS (violet circle) by the product of the pqsH gene (violet arrow), itself positively regulated by LasR. The MvfR regulator (light green star) binds PQS and activates several genes coding for virulence factors, including those for the biosynthesis of pyocyanin (not shown). Likewise, Las and Rhl contribute to the expression of virulence genes. The level of expression of each gene is indicated, and all values are negative except for lasI (unchanged). The HigA antitoxin gene is overexpressed in Pf4*-infected cells and has been shown to bind to the promoter region of the mvfR gene, inhibiting its transcription (128).