title: Lysophosphatidic acid inhibition of the accumulation of Pseudomonas aeruginosa PAO1 alginate, pyoverdin, elastase and LasA.
abstract: The pathogenesis of Pseudomonas aeruginosa is at least partially attributable to its ability to synthesize and secrete the siderophore pyoverdin and the two zinc metalloproteases elastase and LasA, and its ability to form biofilms in which bacterial cells are embedded in an alginate matrix. In the present study, a lysophospholipid, 1-palmitoyl-2-hydroxy-sn-glycero-3-phosphate [also called monopalmitoylphosphatidic acid (MPPA)], which accumulates in inflammatory exudates, was shown to inhibit the extracellular accumulation of P. aeruginosa PAO1 alginate, elastase, LasA protease and the siderophore pyoverdin. MPPA also inhibited biofilm formation. The inhibitory effects of MPPA occur independently of rpoS expression and without affecting the accumulation of the autoinducers N-(3-oxododecanoyl) homoserine lactone and N-butyryl-L-homoserine lactone, and may be due, at least in part, to the ability of MPPA to bind divalent cations.
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA1.
authors.forename: David C
authors.initials: DC
authors.lastname: Laux
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA1.
authors.forename: Joy M
authors.initials: JM
authors.lastname: Corson
authors.affiliation: Biocentrum, Bldg 301, Technical University of Denmark, DK-2800 Lyngby, Denmark2.
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
authors.affiliation: Biocentrum, Bldg 301, Technical University of Denmark, DK-2800 Lyngby, Denmark2.
authors.forename: Morten
authors.initials: M
authors.lastname: Hentzer
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA1.
authors.forename: Annette
authors.initials: A
authors.lastname: Møller
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA1.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Wosencroft
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA3.
authors.forename: Joan C
authors.initials: JC
authors.lastname: Olson
authors.affiliation: Department of Gastrointestinal Infections, Statens Serum Institut, DK 2300 Copenhagen, Denmark4.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Krogfelt
authors.affiliation: Department of Microbiology, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA5.
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Goldberg
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA1.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Cohen
mesh_terms: D000464:Alginates / Q000378:metabolism*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D004492:Edetic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020689:Exopeptidases / Q000096:biosynthesis / Q000378:metabolism; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D008246:Lysophospholipids / Q000494:pharmacology*; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology; D019081:O Antigens / Q000096:biosynthesis / Q000378:metabolism; D009842:Oligopeptides; D010860:Pigments, Biological / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D017262:Siderophores / Q000378:metabolism; D012808:Sigma Factor / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000464:Alginates; D001426:Bacterial Proteins; D006603:Hexuronic Acids; D008246:Lysophospholipids; D008670:Metals; D019081:O Antigens; D009842:Oligopeptides; D010860:Pigments, Biological; D017262:Siderophores; D012808:Sigma Factor; C069567:sigma factor KatF protein, Bacteria; C042453:pyoverdin; D020723:Glucuronic Acid; D004492:Edetic Acid; D020689:Exopeptidases; D008666:Metalloendopeptidases; C066371:staphylolytic protease