Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa

Abstract

Numerous species of bacteria use an elegant regulatory mechanism known as quorum sensing to control the expression of specific genes in a cell-density dependent manner. In Gram-negative bacteria, quorum sensing systems function through a cell-to-cell signal molecule (autoinducer) that consists of a homoserine lactone with a fatty acid side chain. Such is the case in the opportunistic human pathogen Pseudomonas aeruginosa, which contains two quorum sensing systems (las and rhl) that operate via the autoinducers, N-(3-oxododecanoyl)-L-homoserine lactone and N-butyryl-Lhomoserine lactone. The study of these signal molecules has shown that they bind to and activate transcriptional activator proteins that specifically induce numerous P. aeruginosa virulence genes. We report here that P. aeruginosa produces another signal molecule, 2-heptyl-3-hydroxy-4-quinolone, which has been designated as the Pseudomonas quinolone signal. It was found that this unique cell-to-cell signal controlled the expression of lasB, which encodes for the major virulence factor, LasB elastase. We also show that the synthesis and bioactivity of Pseudomonas quinolone signal were mediated by the P. aeruginosa las and rhl quorum sensing systems, respectively. The demonstration that 2-heptyl-3-hydroxy-4-quinolone can function as an intercellular signal sheds light on the role of secondary metabolites and shows that P. aeruginosa cell-to-cell signaling is not restricted to acyl-homoserine lactones.

Proteomic analysis of Pseudomonas aeruginosa grown under magnesium limitation

“…aeruginosa PAO-1 was grown overnight at 37°C in N-medium supplemented with either 8 M or 1 mM MgSO 4 . PQS was extracted from bacterial cultures by acidified ethyl acetate as described [18,19] and separated on TLC plates (20 ϫ 20 cm silica gel 60 F 254 ; EM Science). Culture extracts were separated with the 17:2:1 methylene chloride/acetonitrile/dioxane solvent.…”

“…Furthermore, proteins regulated by quorum sensing such as rhamnosyltransferase and enzymes of both P. aeruginosa phenazine antibiotic biosynthesis operons were repressed during growth in low magnesium (Table 2). Recently, a non-HSL P. aeruginosa intercellular signal, 2-heptyl 3-hydroxy 4-quinolone (PQS, Pseudomonas quinolone signal), a component of the P. aeruginosa quorum sensing hierarchy, has been described [19]. A chromosomal region encoding five proteins (PA0996 -1000) was recently shown to be essential for the production of PQS [30,31].…”

Anaerobiosis-Induced Loss of Cytotoxicity Is Due to Inactivation of Quorum Sensing in Pseudomonas aeruginosa

“…P. aeruginosa QS is also regulated by another system, which involves potentiation of transcriptional activation by MvfR (also known as PqsR) upon binding of a Pseudomonas quinolone signal (PQS) (55). The PQS/MvfR complex actively participates in the intertwined P. aeruginosa QS network, and accumulating evidence now suggests that PQS-mediated QS is absolutely required for the uninterrupted production of elastase (29,36).…”

Pseudomonas Quinolone Signal Affects Membrane Vesicle Production in not only Gram-Negative but also Gram-Positive Bacteria

“…We investigated whether PQS induces MV production in E. coli K12. PQS has been known to accumulate at 50 µM in the supernatant of P. aeruginosa cultures (31). Consequently, PQS was added to E. coli cultures at 0, 20 or 50 µM (final concentration), and growth curves were examined (Fig.…”

“…In addition, P. aeruginosa uses a non-AHL quorum-sensing signal, 2-heptyl-3-hydroxy-4-quinolone (the Pseudomonas quinolone signal: PQS) (31). P. aeruginosa produces a variety of 2-alkyl-4-quinolones (AHQs), a class of antimicrobials to which PQS belongs (22).…”