Haemodynamic effects of the bacterial quorum sensing signal molecule, N‐(3‐oxododecanoyl)‐L‐homoserine lactone, in conscious, normal and endotoxaemic rats

Abstract

1 N-acylhomoserine lactones (AHLs) are small, diusible signalling molecules, employed by Gramnegative bacteria to coordinate gene expression with cell population density. Recent in vitro ®ndings indicate that AHLs may function as virulence determinants per se, through modi®cation of cytokine production by eukaryotic cells, and by stimulating the relaxation of blood vessels. 2 In the present study, we assessed the in¯uence of AHLs on cardiovascular function in conscious rats, and draw attention to the ability of the N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), a signal molecule produced by P. aeruginosa, to cause marked bradycardia. This bradycardic eect was blocked by atropine and atenolol, and did not occur in vitro. Furthermore, modi®cation of the acyl side chain length resulted in the loss of activity, whereas removal of the homoserine lactone ring, did not. The bradycardic eect of 3-oxo-C12-HSL was also observed in endotoxaemic animals, albeit attenuated. 3 In normal rats, 3-oxo-C12-HSL caused initial mesenteric and hindquarters vasoconstriction, but only slight, and delayed signs of vasodilatation in the renal and mesenteric vascular beds. Furthermore, administration of 3-oxo-C12-HSL (pre-treatment or 2 h post-treatment) together with LPS, did not modify the established regional haemodynamic eects of the LPS, 6 h after the onset of its infusion. 4 Our observations do not provide any clear evidence for an ability of 3-oxo-C12-HSL to modify the haemodynamic responses to LPS infusion. However, they are not inconsistent with the hypothesis that some of the cardiovascular sequelae of bacterial infection may be modulated by an in¯uence of bacterial quorum sensing signalling molecules on the host.

Quorum Sensing inYersinia enterocoliticaControls Swimming and Swarming Motility

“…3-Oxo-C12-HSL also exerts a profound effect on heart rate, inducing bradycardia in live conscious rats (12). In addition both 3-oxo-C10-HSL and 3-oxo-C14-HSL also exhibit similar albeit reduced immunemodulatory activity (7).…”

Modification of In Vivo and In Vitro T- and B-Cell-Mediated Immune Responses by thePseudomonas aeruginosaQuorum-Sensing MoleculeN-(3-Oxododecanoyl)-l-Homoserine Lactone

“…Other complicating factors of the in vivo experiments are the potential for OdDHL to be acting on cell types other than the T cells and antigenpresenting cells present in the in vitro cultures and the reported instability of OdDHL under physiological conditions (55). For example, there are reports of OdDHL affecting the function of cell types as diverse as vascular smooth muscle cells (13,20), epithelial cells (7,46,47), and fibroblasts (46,48), all of which could be involved in an in vivo model, as well as the immune cells present in the in vitro model systems (47,51). In addition, some effects of OdDHL appear to depend on the context in which cells are studied.…”

LuxS: its role in central metabolism and the in vitro synthesis of 4-hydroxy-5-methyl-3(2H)-furanone

“…AHL molecules accumulate during the growth of a bacterial population and activate transcriptional regulators of the LuxR family once a critical concentration has been reached. Besides their role as signal molecules, some AHLs may also act as virulence factors (Telford et al, 1998 ;Gardiner et al, 2001). …”