Revisiting quorum sensing: Discovery of additional chemical and biological functions for 3-oxo- N -acylhomoserine lactones

Abstract

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.tetramic acid ͉ bactericidal agents ͉ evolution

Quorum quenching enzyme activity is widely conserved in the sera of mammalian species

“…For example, AiiA, an AHL-lactonase enzyme coded by the aiiA gene from Bacillus sp., can hydrolyze the lactone ring of AHL signals [10]. Evidence suggests that Bacillus may adopt this ability to boost its competitive strength in ecosystems [11], as some bacterial species use AHL signals to coordinate antibiotic production and the signals could spontaneously convert to bactericidal compounds [12,13]. Intriguingly, AHL inactivation activity has also been found recently in human epithelia cells and plant seedlings [14,15], implying that QS interference may also be one of innate defense mechanisms of higher organisms against microbial infections.…”

Outcome and Prevention of Pseudomonas aeruginosa-Staphylococcus aureus Interactions During Pulmonary Infections in Cystic Fibrosis

“…The 3-oxo-C12-HSL also modulates the production of S. aureus exotoxins and cell-surface proteins through the repression of sarA and agr by interaction with a specific and saturable receptor(s) at the cytoplasmic membrane. Furthermore, the 3-oxo-C12-HSL is capable of undergoing internal re-arrangement to form the 3-oxo-C12-tetrameric acid, which also has an inhibitory activity against Grampositive bacteria (Kaufmann et al, 2005). A recent study investigated the formation of biofilms by P. aeruginosa-S. aureus co-cultures using a flow chamber system and confocal microscopy .…”

Entrainment and Control of Bacterial Populations: An in Silico Study over a Spatially Extended Agent Based Model

“…Units Value Basal production rates LI [21] a 0 L µM.min −1 7.79E-6 aA [21] a 0 A µM.min −1 6.18E-6 Active production rates LI [21] k p LI µM.min −1 9.00E-1 aA [21] k p aA µM.min −1 9.00E-1 Cell reaction rates AHL production rate [50,51] kp 2 min −1 0.90E1 LuxR AHL complex association [52] k r 1+ µM −1 min −1 5.99E-5 LuxR AHL complex dissociation [52] k r 1− min −1 6.00E-6 AHL:aA complex catalytic rate [53] k cat aA min −1 2.6314E3 AHL conc. adjustment for environment [54] η env min −1 3.00E-5 AHL membrane diffusion constant [22,54] η cell min −1 0.300E1 Mean cell radius growth rate − µm.min −1 3.144E-1 Michaelis-Menten constants L:A complex [52] K m LA µM 1.00E-2 aA complex [53] K m aA µM 1.20E3 Degradation related parameters L:A complex [55][56][57] τ LA min −1 2.40E-2 AHL [58] τ A /τà min −1 2.76E-3 Enzymatic degradation related parameters Inverse of K M clx [35,37,59] [35,37,59] [35,37,59] δ 2 µM −1 min −1 2.34E-2 Brownian diffusion AHL Brownian diffusion constant Dà µm 2 sec −1 1.59E2 Table S1. Values and units of parameters used in the model.…”