Figure 4.

Schematic of P. aeruginosa virulence activation pathways due to bacterial sensing of low phosphate. Low phosphate in the mucous layer of the intestine is sensed by P. aeruginosa through PstS protein. This activation of PstS results in changes in the Pst-PhoU-PhoR complex, leading to histidine kinase PhoR phosphorylation and activation of the transcriptional regulator PhoB that then binds to the pho box gene sequence that controls hundreds of genes including those encoding main regulators of quorum sensing, such as MvfR. MvfR is a transcriptional regulator that acts upstream of the operon pqsABCDE, which codes for, among other things, the enzymes that lead to the production of PQS, a quorum sensing compound, and the bactericidal compound HQNO. PQS serves three additional functions: 1) activates lecA, which leads to the production of PAI-lectin, 2) is secreted to bind to free iron (Fe), and 3) feeds back to enhance the binding of MvfR to the promoter sequence upstream of pqsABCDE. All the above molecular components are represented by state variables in the GMABM, and the directional arrows indicate the presence of state transition rules.