title: Natriuretic peptides affect Pseudomonas aeruginosa and specifically modify lipopolysaccharide biosynthesis.
abstract: Natriuretic peptides of various forms are present in animals and plants, and display structural similarities to cyclic antibacterial peptides. Pretreatment of Pseudomonas aeruginosa PAO1 with brain natriuretic peptide (BNP) or C-type natriuretic peptide (CNP) increases bacterium-induced glial cell necrosis. In eukaryotes, natriuretic peptides act through receptors coupled to cyclases. We observed that stable analogs of cAMP (dibutyryl cAMP) and cGMP (8-bromo-cGMP) mimicked the effect of brain natriuretic peptide and CNP on bacteria. Further evidence for the involvement of bacterial cyclases in the regulation of P. aeruginosa PAO1 cytotoxicity by natriuretic peptides is provided by the observed doubling of intrabacterial cAMP concentration after exposure to CNP. Lipopolysaccharide (LPS) extracted from P. aeruginosa PAO1 treated with both dibutyryl cAMP and 8-bromo-cGMP induces higher levels of necrosis than LPS extracted from untreated bacteria. Capillary electrophoresis and MALDI-TOF MS analysis have shown that differences in LPS toxicity are due to specific differences in the structure of the macromolecule. Using a strain deleted in the vfr gene, we showed that the Vfr protein is essential for the effect of natriuretic peptides on P. aeruginosa PAO1 virulence. These data support the hypothesis that P. aeruginosa has a cyclic nucleotide-dependent natriuretic peptide sensor system that may affect virulence by activating the expression of Vfr and LPS biosynthesis.
authors.affiliation: Laboratory of Cold Microbiology, UPRES 2123, University of Rouen, Evreux, France.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Veron
authors.forename: Olivier
authors.initials: O
authors.lastname: Lesouhaitier
authors.forename: Xaviera
authors.initials: X
authors.lastname: Pennanec
authors.forename: Karine
authors.initials: K
authors.lastname: Rehel
authors.forename: Philippe
authors.initials: P
authors.lastname: Leroux
authors.forename: Nicole
authors.initials: N
authors.lastname: Orange
authors.forename: Marc G J
authors.initials: MG
authors.lastname: Feuilloley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D019075:Electrophoresis, Capillary; D008070:Lipopolysaccharides / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D045265:Natriuretic Peptides / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008070:Lipopolysaccharides; D045265:Natriuretic Peptides; D000242:Cyclic AMP; D006152:Cyclic GMP