title: Pseudomonas aeruginosa lipopolysaccharide: a major virulence factor, initiator of inflammation and target for effective immunity.
abstract: Pseudomonas aeruginosa is one of the most important bacterial pathogens encountered by immunocompromised hosts and patients with cystic fibrosis (CF), and the lipopolysaccharide (LPS) elaborated by this organism is a key factor in virulence as well as both innate and acquired host responses to infection. The molecule has a fair degree of heterogeneity in its lipid A and O-antigen structure, and elaborates two different outer-core glycoforms, of which only one is ligated to the O-antigen. A close relatedness between the chemical structures and genes encoding biosynthetic enzymes has been established, with 11 major O-antigen groups identified. The lipid A can be variably penta-, hexa- or hepta-acylated, and these isoforms have differing potencies when activating host innate immunity via binding to Toll-like receptor 4 (TLR4). The O-antigen is a major target for protective immunity as evidenced by numerous animal studies, but attempts, to date, to produce a human vaccine targeting these epitopes have not been successful. Newer strategies employing live attenuated P. aeruginosa, or heterologous attenuated bacteria expressing P. aeruginosa O-antigens are potential means to solve some of the existing problems related to making a P. aeruginosa LPS-specific vaccine. Overall, there is now a large amount of information available about the genes and enzymes needed to produce the P. aeruginosa LPS, detailed chemical structures have been determined for the major O-antigens, and significant biologic and immunologic studies have been conducted to define the role of this molecule in virulence and immunity to P. aeruginosa infection.
authors.affiliation: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. gpier@channing.harvard.edu
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Pier
mesh_terms: D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology*; D011552:Pseudomonas Infections / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D037521:Virulence Factors