Pseudomonas aeruginosa Overrides the Virulence Inducing Effect of Opioids When It Senses an Abundance of Phosphate
Figure 5
Proposed circumstances under which P. aeruginosa is exposed to opioids and phosphate depletion during stress and mechanisms of phosphate-dependent virulence activation or suppression.
Critical care treatment destabilizes the indigenous microbiota which becomes replaced by pathogens such as P. aeruginosa that colonize the distal gut. Processed foods or parenteral nutrition leads to nutrient limitation in the distal gut where pathogenesis develops. Physiologic stress, pain, and use of analgesics (opioids) coupled with nutrient limitation, promotes premature activation of the MvfR regulated pqsABCDE operon leading to the expression of multiple virulent and antibiotic resistant genes mediated by PqsE. When phosphate is abundant expression of these genes is suppressed in P. aeruginosa. Mechanisms may include suppression of the PstS-PhoB phosphosensory/phosphoregulatory system that involves phosphate binding to PstS, stabilization of Pst-PhoU-PhoR complex, inability of PhoR to phosphorylate PhoB, and inactivation of the PHO operon including MvfR.