Revisiting quorum sensing: Discovery of additional chemical and biological functions for 3-oxo-N-acylhomoserine lactones.
Bacteria use small diffusible molecules to exchange information in a process called quorum sensing. An important class of autoinducers used by Gram-negative bacteria is the family of N-acylhomoserine lactones. Here, we report the discovery of a previously undescribed nonenzymatically formed product from N-(3-oxododecanoyl)-L-homoserine lactone; both the N-acylhomoserine and its novel tetramic acid degradation product, 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione, are potent antibacterial agents. Bactericidal activity was observed against all tested Gram-positive bacterial strains, whereas no toxicity was seen against Gram-negative bacteria. We propose that Pseudomonas aeruginosa utilizes this tetramic acid as an interference strategy to preclude encroachment by competing bacteria. Additionally, we have discovered that this tetramic acid binds iron with comparable affinity to known bacterial siderophores, possibly providing an unrecognized mechanism for iron solubilization. These findings merit new attention such that other previously identified autoinducers be reevaluated for additional biological functions.
Kaufmann
Gunnar F
GF
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Sartorio
Rafaella
R
Lee
Sang-Hyeup
SH
Rogers
Claude J
CJ
Meijler
Michael M
MM
Moss
Jason A
JA
Clapham
Bruce
B
Brogan
Andrew P
AP
Dickerson
Tobin J
TJ
Janda
Kim D
KD
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D011760:Pyrrolidinones / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*
D011760:Pyrrolidinones; C088386:homoserine lactone; C009435:tetramic acid; D007501:Iron; D015107:4-Butyrolactone