Bactericidal properties of group IIa secreted phospholipase A(2) against Pseudomonas aeruginosa clinical isolates.
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.
Dubouix
Anne
A
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.
Campanac
Catherine
C
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.
Fauvel
Josette
J
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.
Simon
Marie-Françoise
MF
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.
Salles
Jean-Pierre
JP
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.
Roques
Christine
C
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.
Chap
Hugues
H
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.
Marty
Nicole
N
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.
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
D010743:Phospholipids; D012965:Sodium Chloride; D010741:Phospholipases A; D054501:Group II Phospholipases A2