title: Persistent cystic fibrosis isolate Pseudomonas aeruginosa strain RP73 exhibits an under-acylated LPS structure responsible of its low inflammatory activity.
abstract: Pseudomonas aeruginosa, the major pathogen involved in lethal infections in cystic fibrosis (CF) population, is able to cause permanent chronic infections that can persist over the years. This ability to chronic colonize CF airways is related to a series of adaptive bacterial changes involving the immunostimulant lipopolysaccharide (LPS) molecule. The structure of LPSs isolated from several P. aeruginosa strains showed conserved features that can undergo chemical changes during the establishment of the chronic infection. In the present paper, we report the elucidation of the structure and the biological activity of the R-LPS (lipooligosaccharide, LOS) isolated from the persistent CF isolate P. aeruginosa strain RP73, in order to give further insights in the adaptation mechanism of the pathogen in the CF environment. The complete structural analysis of P. aeruginosa RP73 LOS was achieved by chemical analyses, NMR spectroscopy and MALDI MS spectrometry, while the assessment of the biological activity was attained testing the in vivo pro-inflammatory capacity of the isolated LOS molecule. While a typical CF LPS is able to trigger a high immune response and production of pro-inflammatory molecules, this P. aeruginosa RP73 LOS showed to possess a low pro-inflammatory capacity. This was possible due to a singular chemical structure possessing an under-acylated lipid A very similar to the LPS of P. aeruginosa found in chronic lung diseases such as bronchiectstasis.
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Napoli "Federico II", Complesso Universitario Monte S. Angelo, Via Cintia 4, 80126 Napoli, Italy.
authors.forename: Flaviana
authors.initials: F
authors.lastname: Di Lorenzo
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Napoli "Federico II", Complesso Universitario Monte S. Angelo, Via Cintia 4, 80126 Napoli, Italy.
authors.forename: Alba
authors.initials: A
authors.lastname: Silipo
authors.affiliation: Infection and Cystic Fibrosis Unit, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Bianconi
authors.affiliation: Infection and Cystic Fibrosis Unit, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Nicola Ivan
authors.initials: NI
authors.lastname: Lore'
authors.affiliation: Istituto di Chimica e Tecnologia dei Polimeri - ICTP - CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scamporrino
authors.affiliation: Istituto di Chimica e Tecnologia dei Polimeri - ICTP - CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sturiale
authors.affiliation: Istituto di Chimica e Tecnologia dei Polimeri - ICTP - CNR, Via P. Gaifami 18, 95126 Catania, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Garozzo
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Napoli "Federico II", Complesso Universitario Monte S. Angelo, Via Cintia 4, 80126 Napoli, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Lanzetta
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Napoli "Federico II", Complesso Universitario Monte S. Angelo, Via Cintia 4, 80126 Napoli, Italy.
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Parrilli
authors.affiliation: Infection and Cystic Fibrosis Unit, San Raffaele Scientific Institute, Milano, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bragonzi
authors.affiliation: Dipartimento di Scienze Chimiche, Università di Napoli "Federico II", Complesso Universitario Monte S. Angelo, Via Cintia 4, 80126 Napoli, Italy. Electronic address: molinaro@unina.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molinaro
mesh_terms: D000215:Acylation; D000818:Animals; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D003550:Cystic Fibrosis / Q000382:microbiology* / Q000473:pathology; D007249:Inflammation / Q000382:microbiology* / Q000473:pathology*; D008050:Lipid A / Q000737:chemistry / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D009195:Peroxidase / Q000378:metabolism; D066244:Proton Magnetic Resonance Spectroscopy; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification* / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008050:Lipid A; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; D009195:Peroxidase
keywords: Chronic infections in cystic fibrosis; Cystic fibrosis; Lipid A; Lipopolysaccharide; Pseudomonas aeruginosa; Structural analysis