Our study focused on a Mesorhizobium sp. that is phylogenetically affiliated by 16S rRNA gene sequence to other marine and saline bacteria of this genus. Liquid chromatography-mass spectrometry investigations of the extract obtained from solid-phase extraction of cultures of this bacterium indicated the presence of several N-acyl homoserine lactones (AHLs), with chain lengths of C 10 to C 16 . Chromatographic separation of the active bacterial extract yielded extraordinarily large amounts of two unprecedented acylated homoserine lactones, 5-cis-3-oxo-C 12 -homoserine lactone (5-cis-3-oxo-C 12 -HSL) (compound 1) and 5-cis-C 12 -HSL (compound 2). Quorum-sensing activity of compounds 1 and 2 was shown in two different biosensor systems [Escherichia coli MT102(pSB403) and Pseudomonas putida F117(pKR-C12)]. Furthermore, it was shown that both compounds can restore protease and pyoverdin production of an AHL-deficient Pseudomonas aeruginosa PAO1 lasI rhlI double mutant, suggesting that these signal molecules maybe used for intergenus signaling. In conclusion, these data indicate that the quorum-sensing activity of compounds 1 and 2 is modulated by the chain length and functional groups of the acyl moiety. Additionally, compound 1 showed antibacterial and cytotoxic activities.Homoserine lactones (HSLs) possess, in addition to the lactone moiety, an acyl side chain. The chain length (C 4 to C 18 ), substitution at position 3Ј, and existence of a double bond in the acyl chain vary in naturally occurring HSLs.Bacteria employ sophisticated cell-to-cell communication systems to coordinate their activities and to act in a concerted manner. Gram-negative bacteria produce N-acyl homoserine lactones (AHLs), signal molecules which allow the producer to monitor its own population density in a process known as quorum sensing (QS) (for reviews see references 3, 5, and 39). These regulatory systems typically rely on two proteins, an AHL synthase, which is usually a member of the LuxI family of proteins, and an AHL receptor protein belonging to the LuxR family of transcriptional regulators. At low population densities, cells produce a basal level of AHLs via the activity of the AHL synthase. As the cell density increases, AHLs accumulate in the growth medium. Upon reaching a critical threshold concentration, AHL molecules bind to their cognate receptor, which in turn activates or represses expression of target genes.Compared to the case for bacteria from terrestrial environments, to date relatively little information is available on AHLbased QS systems in marine bacteria. Most notably, however the first organism for which AHL-dependent cell-to-cell signaling was demonstrated was the marine bacterium Vibrio fischeri. Moreover, recent work has shown that AHLs are of major importance for the transcriptional control in many marine Vibrio and Photobacterium species (4), and different Roseobacter strains isolated from marine snow were capable of AHL production (9). In the free-living marine bacterium Rhodobacter sphaeroides, a QS system wa...