Taxonomic group: bacteria / Proteobacteria
(Phylum: Proteobacteria)
Host organism: Homo sapiens
Associated disease: cystic fibrosis (CF) [ICD11:
CA25 
];
infection due to Pseudomonas aeruginosa [ICD11:
XN5L6 ]
The structure was elucidated in this paperNCBI PubMed ID: 20037649Publication DOI: 10.1371/journal.pone.0008439Journal NLM ID: 101285081Publisher: San Francisco, CA: Public Library of Science
Correspondence: bragonzi.alessandra
hsr.it
Institutions: Dipartimento di Chimica Organica e Biochimica, Universita di Napoli Federico II, Napoli, Italy, Infection and Cystic Fibrosis Unit, San Raffaele Scientific Institute, Milano, Italy, Dipartimento di Biologia Cellulare e dello Sviluppo, Sapienza-Università di Roma, Roma, Italy, CEINGE Biotecnologie Avanzate, Napoli, Italy, Instituto Pasteur-Fondazione Cenci Bolognetti, Roma, Italy Universidad Nacional, Costa Ric
Pseudomonas aeruginosa can establish life-long airways chronic infection in patients with cystic fibrosis (CF) with pathogenic variants distinguished from initially acquired strain. Here, we analysed chemical and biological activity of P. aeruginosa Pathogen-Associated Molecular Patterns (PAMPs) in clonal strains, including mucoid and non-mucoid phenotypes, isolated during a period of up to 7.5 years from a CF patient. Chemical structure by MS spectrometry defined lipopolysaccharide (LPS) lipid A and peptidoglycan (PGN) muropeptides with specific structural modifications temporally associated with CF lung infection. Gene sequence analysis revealed novel mutation in pagL, which supported lipid A changes. Both LPS and PGN had different potencies when activating host innate immunity via binding TLR4 and Nod1. Significantly higher NF-kB activation, IL-8 expression and production were detected in HEK293hTLR4/MD2-CD14 and HEK293hNod1 after stimulation with LPS and PGN respectively, purified from early P. aeruginosa strain as compared to late strains. Similar results were obtained in macrophages-like cells THP-1, epithelial cells of CF origin IB3-1 and their isogenic cells C38, corrected by insertion of cystic fibrosis transmembrane conductance regulator (CFTR). In murine model, altered LPS structure of P. aeruginosa late strains induces lower leukocyte recruitment in bronchoalveolar lavage and MIP-2, KC and IL-1β cytokine levels in lung homogenates when compared with early strain. Histopathological analysis of lung tissue sections confirmed differences between LPS from early and late P. aeruginosa. Finally, in this study for the first time we unveil how P. aeruginosa has evolved the capacity to evade immune system detection, thus promoting survival and establishing favourable conditions for chronic persistence. Our findings provide relevant information with respect to chronic infections in CF
Lipopolysaccharide, Pseudomonas aeruginosa, lipid A, cystic fibrosis
Structure type: oligomer
Location inside paper: fig.1C, Hepta
Compound class: lipid A
Contained glycoepitopes: IEDB_135394,IEDB_135515,IEDB_141807,IEDB_151531,IEDB_534864
Methods: SDS-PAGE, DNA techniques, chemical analysis, ELISA, acid hydrolysis, MALDI-MS, MS/MS, genetic methods, RP-HPLC
Biosynthesis and genetic data: genetic data
Comments, role: lipid A obtained from P. aeruginosa clinical strain AA44 isolated from a CF patient after years of chronic infection
Related record ID(s): 23674, 31249, 31250
NCBI Taxonomy refs (TaxIDs): 287
Show glycosyltransferases
There is only one chemically distinct structure:
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