title: Bactericidal properties of group IIa secreted phospholipase A(2) against Pseudomonas aeruginosa clinical isolates.
abstract: It has been shown that human group IIa secreted phospholipase A(2) (sPLA(2)), found at high levels in inflammatory fluids, displays direct bactericidal properties against Gram-positive bacteria, while activity against Gram-negative bacteria requires the complement system or additional co-factors produced by neutrophils. Pseudomonas aeruginosa, an increasingly prevalent opportunistic human pathogen, is the most common Gram-negative rod found in cystic fibrosis lung infections, where it is associated with an inflammatory environment. Because murine intestinal group II sPLA(2) produced by Paneth cells has been shown to be directly bactericidal against Gram-negative bacteria, IIa sPLA(2) activity against P. aeruginosa clinical isolates was evaluated and provides the first evidence that the enzyme can be fully bactericidal in a concentration- and time-dependent manner against Gram-negative rods. Furthermore, it was demonstrated that these bactericidal properties were unaffected by high protein and salt concentrations, as observed in cystic fibrosis secretions, and that bacterial killing paralleled phospholipid hydrolysis. Finally, no cytotoxicity was observed when IIa sPLA(2) was incubated with human pulmonary cells, highlighting its potential use to synergize bactericidal antibiotics by promoting sublethal alterations of the bacterial cell wall.
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Anne
authors: A
authors: Dubouix
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Catherine
authors: C
authors: Campanac
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Josette
authors: J
authors: Fauvel
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Marie-Françoise
authors: MF
authors: Simon
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Jean-Pierre
authors: JP
authors: Salles
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Christine
authors: C
authors: Roques
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Hugues
authors: H
authors: Chap
authors: INSERM CPTP-U563, CHU Purpan, 1 Place du Dr Baylac, TSA 40031, 31059 Toulouse Cedex 9, France 2,4Laboratoire de Bactériologie-Hygiène2 and INSERM U5834, CHU Rangueil, 1 Avenue Jean Poulhes, TSA 50032, 31059 Toulouse Cedex 9, France 3Laboratoire de Microbiologie, Faculté de Pharmacie, 27 Chemin des Maraîchers, 31400 Toulouse, France.
authors: Nicole
authors: N
authors: Marty
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D054501:Group II Phospholipases A2; D006801:Humans; D006868:Hydrolysis; D010741:Phospholipases A / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012965:Sodium Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
chemical_list: D010743:Phospholipids; D012965:Sodium Chloride; D010741:Phospholipases A; D054501:Group II Phospholipases A2