The Oxylipin Dependent Quorum Sensing System enhances Pseudomonas aeruginosa dissemination during burn-associated...

Following severe burn injury, Pseudomonas aeruginosa is the leading cause of life-threatening infection. Herein, we unveil how P. aeruginosa strategically employs host-derived oleic acid, released as consequence of burn-injury, to induce a hypervirulent phenotype via its Oxylipin Dependent Quorum Sensing system (ODS). ODS activation enhanced P. aeruginosa invasion of burned skin and promoted its dissemination to distant organs in vivo. ODS regulation of P. aeruginosa virulence involved the control of nitic oxide levels, a key signaling molecule in bacteria, through upregulation of the nitric oxide reductases NorCB. Immunization with OdsA, one of the enzymes involved in oxylipin generation, or treatment with a pharmacological inhibitor of OdsA, protected mice against lethal P. aeruginosa infection following burn-injury. Our findings reveal a new mechanism underlying P. aeruginosa hypervirulence in burn wounds and identifies OdsA as a promising target for preventing disseminated infections following burns.