title: Dioxygenase-mediated quenching of quinolone-dependent quorum sensing in Pseudomonas aeruginosa.
abstract: 2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) is a quorum-sensing signal molecule used by Pseudomonas aeruginosa. The structural similarity between 3-hydroxy-2-methyl-4(1H)-quinolone, the natural substrate for the 2,4-dioxygenase, Hod, and PQS prompted us to investigate whether Hod quenched PQS signaling. Hod is capable of catalyzing the conversion of PQS to N-octanoylanthranilic acid and carbon monoxide. In P. aeruginosa PAO1 cultures, exogenously supplied Hod protein reduced expression of the PQS biosynthetic gene pqsA, expression of the PQS-regulated virulence determinants lectin A, pyocyanin, and rhamnolipids, and virulence in planta. However, the proteolytic cleavage of Hod by extracellular proteases, competitive inhibition by the PQS precursor 2-heptyl-4(1H)-quinolone, and PQS binding to rhamnolipids reduced the efficiency of Hod as a quorum-quenching agent. Nevertheless, these data indicate that enzyme-mediated PQS inactivation has potential as an antivirulence strategy against P. aeruginosa.
authors.affiliation: School of Molecular Medical Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Pustelny
authors.forename: Alexander
authors.initials: A
authors.lastname: Albers
authors.forename: Klaudia
authors.initials: K
authors.lastname: Büldt-Karentzopoulos
authors.forename: Katja
authors.initials: K
authors.lastname: Parschat
authors.forename: Siri Ram
authors.initials: SR
authors.lastname: Chhabra
authors.forename: Miguel
authors.initials: M
authors.lastname: Cámara
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.forename: Susanne
authors.initials: S
authors.lastname: Fetzner
mesh_terms: D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D015363:Quinolones / Q000737:chemistry / Q000378:metabolism*; D053038:Quorum Sensing / Q000187:drug effects*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D015363:Quinolones; D011994:Recombinant Proteins; D049308:Dioxygenases