title: C-type natriuretic peptide modulates quorum sensing molecule and toxin production in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa coordinates its virulence expression and establishment in the host in response to modification of its environment. During the infectious process, bacteria are exposed to and can detect eukaryotic products including hormones. It has been shown that P. aeruginosa is sensitive to natriuretic peptides, a family of eukaryotic hormones, through a cyclic nucleotide-dependent sensor system that modulates its cytotoxicity. We observed that pre-treatment of P. aeruginosa PAO1 with C-type natriuretic peptide (CNP) increases the capacity of the bacteria to kill Caenorhabditis elegans through diffusive toxin production. In contrast, brain natriuretic peptide (BNP) did not affect the capacity of the bacteria to kill C. elegans. The bacterial production of hydrogen cyanide (HCN) was enhanced by both BNP and CNP whereas the production of phenazine pyocyanin was strongly inhibited by CNP. The amount of 2-heptyl-4-quinolone (HHQ), a precursor to 2-heptyl-3-hydroxyl-4-quinolone (Pseudomonas quinolone signal; PQS), decreased after CNP treatment. The quantity of 2-nonyl-4-quinolone (HNQ), another quinolone which is synthesized from HHQ, was also reduced after CNP treatment. Conversely, both BNP and CNP significantly enhanced bacterial production of acylhomoserine lactone (AHL) [e.g. 3-oxo-dodecanoyl-homoserine lactone (3OC12-HSL) and butanoylhomoserine lactone (C4-HSL)]. These results correlate with an induction of lasI transcription 1 h after bacterial exposure to BNP or CNP. Concurrently, pre-treatment of P. aeruginosa PAO1 with either BNP or CNP enhanced PAO1 exotoxin A production, via a higher toxA mRNA level. At the same time, CNP led to elevated amounts of algC mRNA, indicating that algC is involved in C. elegans killing. Finally, we observed that in PAO1, Vfr protein is essential to the pro-virulent effect of CNP whereas the regulator PtxR supports only a part of the CNP pro-virulent activity. Taken together, these data reinforce the hypothesis that during infection natriuretic peptides, particularly CNP, could enhance the virulence of PAO1. This activity is relayed by Vfr and PtxR activation, and a general diagram of the virulence activation cascade involving AHL, HCN and exotoxin A is proposed.
authors.affiliation: Laboratory of Cold Microbiology - Signals and Micro-environment EA 4312, University of Rouen, 55 Rue Saint Germain, 27000 Evreux, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Blier
authors.affiliation: Laboratory of Cold Microbiology - Signals and Micro-environment EA 4312, University of Rouen, 55 Rue Saint Germain, 27000 Evreux, France.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Veron
authors.affiliation: Laboratoire de Biotechnologie et Chimie Marines, Université de Bretagne-Sud B.P. 92116, 56321 Lorient Cedex, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Bazire
authors.affiliation: Laboratory of Cold Microbiology - Signals and Micro-environment EA 4312, University of Rouen, 55 Rue Saint Germain, 27000 Evreux, France.
authors.forename: Eloïse
authors.initials: E
authors.lastname: Gerault
authors.affiliation: Laboratoire de Biotechnologie et Chimie Marines, Université de Bretagne-Sud B.P. 92116, 56321 Lorient Cedex, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Taupin
authors.affiliation: SIMA, UMR 6014 COBRA, University of Rouen, 27000 Evreux, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Vieillard
authors.affiliation: Laboratoire de Biotechnologie et Chimie Marines, Université de Bretagne-Sud B.P. 92116, 56321 Lorient Cedex, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Rehel
authors.affiliation: Laboratoire de Biotechnologie et Chimie Marines, Université de Bretagne-Sud B.P. 92116, 56321 Lorient Cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Dufour
authors.affiliation: SIMA, UMR 6014 COBRA, University of Rouen, 27000 Evreux, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Le Derf
authors.affiliation: Laboratory of Cold Microbiology - Signals and Micro-environment EA 4312, University of Rouen, 55 Rue Saint Germain, 27000 Evreux, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Orange
authors.affiliation: Laboratory of Cold Microbiology - Signals and Micro-environment EA 4312, University of Rouen, 55 Rue Saint Germain, 27000 Evreux, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Hulen
authors.affiliation: Laboratory of Cold Microbiology - Signals and Micro-environment EA 4312, University of Rouen, 55 Rue Saint Germain, 27000 Evreux, France.
authors.forename: Marc G J
authors.initials: MGJ
authors.lastname: Feuilloley
authors.affiliation: Laboratory of Cold Microbiology - Signals and Micro-environment EA 4312, University of Rouen, 55 Rue Saint Germain, 27000 Evreux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lesouhaitier
mesh_terms: D042462:4-Quinolones / Q000032:analysis; D036002:ADP Ribose Transferases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000382:microbiology; D002373:Cyclic AMP Receptor Protein / Q000235:genetics / Q000378:metabolism; D005098:Exotoxins / Q000096:biosynthesis* / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006856:Hydrogen Cyanide / Q000032:analysis; D008025:Ligases / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D011710:Pyocyanine / Q000096:biosynthesis; D053038:Quorum Sensing; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D042462:4-Quinolones; D036002:ADP Ribose Transferases; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002373:Cyclic AMP Receptor Protein; D005098:Exotoxins; D006856:Hydrogen Cyanide; D008025:Ligases; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type; D011710:Pyocyanine; D012333:RNA, Messenger; D014157:Transcription Factors; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C528166:2-heptyl-4-quinolone; C081237:LasI protein, Pseudomonas aeruginosa; C091090:Vfr protein, Pseudomonas aeruginosa; C073470:LysR protein, Bacteria; C096955:RHLI protein, Pseudomonas aeruginosa