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.
Park
Junguk
J
Department of Chemistry and Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.
Kaufmann
Gunnar F
GF
Bowen
J Phillip
JP
Arbiser
Jack L
JL
Janda
Kim D
KD
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000737:chemistry; D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001000:Ants / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D015964:Gene Expression Regulation, Bacterial; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism / Q000472:pathogenicity; D011710:Pyocyanine / Q000096:biosynthesis; D053038:Quorum Sensing / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D000470:Alkaloids; D001426:Bacterial Proteins; D037521:Virulence Factors; C088386:homoserine lactone; C002351:Solenopsin A; D011710:Pyocyanine; D015107:4-Butyrolactone