Lysophosphatidic acid inhibition of the accumulation of Pseudomonas aeruginosa PAO1 alginate, pyoverdin, elastase and LasA

• Published in: Microbiology (Society for General Microbiology) 2002-06, Vol.148 (6), p.1709-1723
• Main Authors: Laux, David C, Corson, Joy M, Givskov, Michael, Hentzer, Morten, Moller, Annette, Wosencroft, Kathleen A, Olson, Joan C, Krogfelt, Karen A, Goldberg, Joanna B, Cohen, Paul S
• Format: Article
• Language: English
• Subjects: 1-Palmitoyl-2-hydroxy-sn-glycero-3-phosphate; Alginates - metabolism; Bacterial diseases; Bacterial diseases of the respiratory system; Bacterial Proteins - biosynthesis; Bacterial Proteins - genetics; Bacteriology; Biofilms - drug effects; Biofilms - growth & development; Biological and medical sciences; Edetic Acid - pharmacology; elastase; Enzyme Activation - drug effects; Exopeptidases - biosynthesis; Exopeptidases - metabolism; Fundamental and applied biological sciences. Psychology; Glucuronic Acid; Hexuronic Acids; Human bacterial diseases; Infectious diseases; LasA protein; Lysophospholipids - pharmacology; Medical sciences; Metabolism. Enzymes; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - metabolism; Metals - pharmacology; Microbiology; O Antigens - biosynthesis; O Antigens - metabolism; Oligopeptides; Pigments, Biological - metabolism; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - enzymology; Pseudomonas aeruginosa - growth & development; Pseudomonas aeruginosa - metabolism; Siderophores - metabolism; Sigma Factor - biosynthesis; Sigma Factor - genetics
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/00221287-148-6-1709

Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, USA 1 Biocentrum, Bldg 301, Technical University of Denmark, DK-2800 Lyngby, Denmark 2 Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA 3 Department of Gastrointestinal Infections, Statens Serum Institut, DK 2300 Copenhagen, Denmark 4 Department of Microbiology, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA 5 Author for correspondence: Paul S. Cohen. Tel: [phone]. Fax: [phone]. e-mail: pco1697u{at}postoffice.uri.edu 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. Keywords: monopalmitoylphosphatidic acid, cystic fibrosis Abbreviations: BHL, N -butanoyl homoserine lactone; GFP, green fluorescent protein; LB, Luria broth; LPS, lipopolysaccharide; MPPA, 1-palmitoyl-2-hydroxy- sn -glycero-3-phosphate (also known as monopalmitoylphosphatidic acid); OdDHL, N- (3-oxododecanoyl) homoserine lactone