Solenopsin A, a venom alkaloid from the fire ant Solenopsis invicta, inhibits quorum-sensing signaling in Pseudomonas aeruginosa.

In Pseudomonas aeruginosa, quorum-sensing (QS) signaling regulates the expression of virulence factors and thus represents an attractive new target for anti-infective therapy. In the present study, we investigated whether solenopsin A, a venom alkaloid from the fire ant, possessed agonistic or antagonistic QS signaling activity in P. aeruginosa. We evaluated the modulation of virulence factor expression and transcriptional levels of QS-regulated genes in P. aeruginosa by solenopsin A and demonstrated that solenopsin A efficiently disrupted QS signaling. Interestingly, exogenously added C(4)-homoserine lactone (HSL), but not 3-oxo-C(12)-HSL, restored P. aeruginosa QS signaling, suggesting that solenopsin A targets the C(4)-HSL-dependent rhl QS system.