The Bacterial Product Pseudomonas Quinolone Signal Causes Vasorelaxation in Porcine Blood Vessels

Bacteria communicate with each other by releasing chemicals called quorum sensing molecules (QSM). A common gram-negative bacteria, Pseudomonas aeruginosa, releases a number of such molecules including, N-3-(oxododecanoyl)-L-homoserine lactone (3OC12-HSL) and Pseudomonas quinolone signal (2-heptyl-3,4-dihydroxyquinoline, PQS) (1,2). We have previously shown that 3OC12-HSL causes vasorelaxation in the porcine coronary artery (PCA) (3). This study assessed whether PQS also has the capacity to modify vascular function in host tissue.

Pig hearts and spleen were obtained from a local abattoir. Contraction-based studies using isometric tension recording were used. Each organ bath contained Krebs-Henseleit solution, maintained at 37 °C and gassed with 95% O2:5% CO2. Each preparation was exposed to KCl (60 mM) to assess tissue viability, then pre-contracted with U46619 (5-30 nM) to produce 40-70% of the response to KCl. When the appropriate level of U46619-induced tone had been obtained, PQS (0.1-30 µM) or 3OC12-HSL (1-30 µM) were added cumulatively, at 20 minute intervals, or after the response to any given concentration had achieved steady state. The negative logarithm of the PQS or 3OC12-HSL concentration that resulted in a 50% decrease in vasoconstrictor tone (pIC50) was determined. All values were expressed as the standard error of the mean (S.E.M) of observation in tissues from different animals (n). A student’s paired t-test was used to assess the statistical significance (p < 0.05) of any differences between mean values.

PQS inhibited vasoconstrictor tone of porcine isolated coronary artery;the relaxation effect to the maximum PQS concentration used (30 µM) was -79.2 ± 6.5%, while the solvent (Dimethyl sulfoxide) produced a change of -15.2 ± 4.9%, (n=7), (P <0.0001). The relaxation response to the maximum concentration of 3OC12-HSL used (30 µM) was similar in magnitude to PQS i.e. -83.5 ± 3.8 %, while the solvent (acetonitrile) was with a change of -7.7 ± 3.3%,(n=6), (P <0.0001). PQS and 3OC12-HSL also reversed U46619-induced contraction in porcine splenic arteries (PSA) and veins (PSV) (Table 1).

Table 1 The effect of PQS and 3OC12-HSL on porcine coronary artery, splenic artery and vein.

In conclusion, both PQS and 3OC12-HSL caused vasorelaxation in arterial and venous preparations isolated from pigs. PQS was slightly more potent (pIC50) as a vasorelaxant than 3OC12-HSL. These data indicate that a variety of QSM are capable of modifying the host vascular system, which may contribute to bacterial virulence.

(1) Pearson et al (1994) Proc Natl Acad Sci U S A, 91, 197-201.

(2) Diggle et al (2006) Int J Med Microbiol, 296, 83-91.

(3) Lawrence et al (1999) Br J Pharmacol, 128, 845-8.