Abstract
P. aeruginosa produce N-3-oxododecanoyl homoserine lactone (3OC12-HSL), a so-called “quorum-sensing molecule” that provides signals for the production of virulence factors and for bacterial biofilm formation in a paracrine manner. We now found that 3OC12-HSL, but not its 3-deoxo-isomer or acyl homoserine lactones with shorter fatty acids, is also able to activate human polymorphonuclear neutrophils (PMN) in vitro: 3OC12-HSL enhanced the phagocytosis of opsonised bacteria in vitro; up-regulated the surface expression of phagocytosis-related receptors, and was chemotactic for PMN. Because induction of chemotaxis implies the polarisation of the cell by receptors expressed on the surface, we performed uptake studies with radiolabelled 3OC12-HSL. At 4° C we found saturable binding of the radiolabelled 3OC12-HSL, which could be inhibited by an excess of unlabelled 3OC12-HSL, indicating specificity of binding, and hence expression of a distinct surface receptor. By use of selective inhibitors, a signalling pathway, comprising phosphotyrosine kinases, phospholipase C, protein kinase C, mitogen activated protein kinase C was delineated, but in contrast to the well-studied chemokines C5a and interleukin 8, the chemotaxis in response to 3OC12-HSL did not depend on pertussis toxin-sensitive G proteins. Selective surface receptors for 3OC12-HSL have been identified in various bacteria species, but scrutinising a human gene bank did not reveal homologous structures. While the characterisation of the surface receptor awaits further studies, the functional consequence of the cross-kingdom signalling is obvious: by recognising and responding to 3OC12-HSL PMN are attracted to the site of a developing biofilm, and thus may prevent its progression and by that persistent infection.
Correspondence should be addressed to Vienna Medical Academy, Alser Strasse 4, A-1090 Vienna, Austria. Phone: +43 1 4051383 0, Fax: +43 1 4078274, Email: ebjis2009@medacad.org
