The Complete Structure and Pro‐inflammatory Activity of the Lipooligosaccharide of the Highly Epidemic and Virulent Gram‐Negative Bacterium Burkholderia cenocepacia ET‐12 (Strain J2315)

Chemistry - A European Journal - Tập 13 Số 12 - Trang 3501-3511 - 2007
Alba Silipo1, Antonio Molinaro1, Teresa Ieranò1, Anthony De Soyza2, Luisa Sturiale3, Domenico Garozzo3, Christine Aldridge4, Paul A. Corris2, C. M. Anjam Khan4, Rosa Lanzetta1, Michelangelo Parrilli1
1Dipartimento di Chimica Organica e Biochimica, Università di Napoli, Complesso Universitario Monte Sant'angelo, Via Cintia 4, 80126 Napoli, Italy, Fax: (+39) 081‐674‐393
2Transplantation and Immunobiology Group, The Freeman Hospital, High Heaton, Newcastle upon Tyne NE7 7DN, UK
3Istituto per la Chimica e la Tecnologia dei Materiali Polimerici, ICTMP‐CNR, Catania, Italy
4Institute for Cell and Molecular Biosciences, The Medical School, University of Newcastle, Newcastle, UK

Tóm tắt

AbstractMembers of genus Burkholderia include opportunistic Gram‐negative bacteria that are responsible for serious infections in immunocompromised and cystic fibrosis (CF) patients. The Burkholderia cepacia complex is a group of microorganisms composed of at least nine closely related genomovars. Among these, B. cenocepacia is widely recognized to cause epidemics associated with excessive mortality. Species that belong to this strain are problematic CF pathogens because of their high resistance to antibiotics, which makes respiratory infections difficult to treat and impossible to eradicate. Infection by these bacteria is associated with higher mortality in CF and poor outcomes following lung transplantation. One virulence factor contributing to this is the pro‐inflammatory lipopolysaccharide (LPS) molecules. Thus, the knowledge of the lipopolysaccharide structure is an essential prerequisite to the understanding of the molecular mechanisms involved in the inflammatory process. Such data are instrumental in aiding the design of antimicrobial compounds and for developing therapeutic strategies against the inflammatory cascade. In particular, defining the structure of the LPS from B. cenocepacia ET‐12 clone LMG 16656 (also known as J2315) is extremely important given the recent completion of the sequencing project at the Sanger Centre using this specific strain. In this paper we address this issue by defining the pro‐inflammatory activity of the pure lipopolysaccharide, and by describing its full primary structure. The activity of the lipopolysaccharide was tested as a stimulant in human myelomonocytic U937 cells. The structural analysis was carried out by compositional analysis, mass spectrometry and 2D NMR spectroscopy on the intact lipooligosacchride (LOS) and its fragments, which were obtained by selective chemical degradations.

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Chemistry - A European Journal

Tập 13 Số 12

3501-3511

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