Pseudomonas Aeruginosa Lipopolysaccharide: a Major Virulence Factor, Initiator of Inflammation and Target for Effective Immunity

Overview

Journal Int J Med Microbiol

Specialty Microbiology

Date 2007 May 1

PMID 17466590

Citations 121

Authors

Gerald B Pier

Affiliations

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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.

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References

Lyczak J, Cannon C, Pier G . Lung infections associated with cystic fibrosis. Clin Microbiol Rev. 2002; 15(2):194-222. PMC: 118069. DOI: 10.1128/CMR.15.2.194-222.2002. View

Bystrova O, Shashkov A, Kocharova N, Knirel Y, Lindner B, Zahringer U . Structural studies on the core and the O-polysaccharide repeating unit of Pseudomonas aeruginosa immunotype 1 lipopolysaccharide. Eur J Biochem. 2002; 269(8):2194-203. DOI: 10.1046/j.1432-1033.2002.02875.x. View

Schroeder T, Lee M, Yacono P, Cannon C, Alev Gerceker A, Golan D . CFTR is a pattern recognition molecule that extracts Pseudomonas aeruginosa LPS from the outer membrane into epithelial cells and activates NF-kappa B translocation. Proc Natl Acad Sci U S A. 2002; 99(10):6907-12. PMC: 124502. DOI: 10.1073/pnas.092160899. View

Reeves P, Wang L . Genomic organization of LPS-specific loci. Curr Top Microbiol Immunol. 2002; 264(1):109-35. View

Obritsch M, Fish D, MacLaren R, Jung R . Nosocomial infections due to multidrug-resistant Pseudomonas aeruginosa: epidemiology and treatment options. Pharmacotherapy. 2005; 25(10):1353-64. DOI: 10.1592/phco.2005.25.10.1353. View

Steuhl K, DORING G, Henni A, Thiel H, Botzenhart K . Relevance of host-derived and bacterial factors in Pseudomonas aeruginosa corneal infections. Invest Ophthalmol Vis Sci. 1987; 28(9):1559-68. View

Powderly W, Schreiber J, Pier G, Markham R . T cells recognizing polysaccharide-specific B cells function as contrasuppressor cells in the generation of T cell immunity to Pseudomonas aeruginosa. J Immunol. 1988; 140(8):2746-52. View

Jeffery P, Brain A . Surface morphology of human airway mucosa: normal, carcinoma or cystic fibrosis. Scanning Microsc. 1988; 2(1):553-60. View

Cryz Jr S, Sadoff J, Ohman D, Furer E . Characterization of the human immune response to a Pseudomonas aeruginosa O-polysaccharide-toxin A conjugate vaccine. J Lab Clin Med. 1988; 111(6):701-7. View

10.

Coyne Jr M, Russell K, Coyle C, Goldberg J . The Pseudomonas aeruginosa algC gene encodes phosphoglucomutase, required for the synthesis of a complete lipopolysaccharide core. J Bacteriol. 1994; 176(12):3500-7. PMC: 205537. DOI: 10.1128/jb.176.12.3500-3507.1994. View

11.

Dean C, Goldberg J . Pseudomonas aeruginosa galU is required for a complete lipopolysaccharide core and repairs a secondary mutation in a PA103 (serogroup O11) wbpM mutant. FEMS Microbiol Lett. 2002; 210(2):277-83. DOI: 10.1111/j.1574-6968.2002.tb11193.x. View

12.

Raymond C, Sims E, Kas A, Spencer D, Kutyavin T, Ivey R . Genetic variation at the O-antigen biosynthetic locus in Pseudomonas aeruginosa. J Bacteriol. 2002; 184(13):3614-22. PMC: 135118. DOI: 10.1128/JB.184.13.3614-3622.2002. View

13.

Khatri S, Lass J, Heinzel F, Petroll W, Gomez J, Diaconu E . Regulation of endotoxin-induced keratitis by PECAM-1, MIP-2, and toll-like receptor 4. Invest Ophthalmol Vis Sci. 2002; 43(7):2278-84. View

14.

Poschet J, Perkett E, Deretic V . Hyperacidification in cystic fibrosis: links with lung disease and new prospects for treatment. Trends Mol Med. 2002; 8(11):512-9. DOI: 10.1016/s1471-4914(02)02414-0. View

15.

Coleman F, Mueschenborn S, Meluleni G, Ray C, Carey V, Vargas S . Hypersusceptibility of cystic fibrosis mice to chronic Pseudomonas aeruginosa oropharyngeal colonization and lung infection. Proc Natl Acad Sci U S A. 2003; 100(4):1949-54. PMC: 149939. DOI: 10.1073/pnas.0437901100. View

16.

Priebe G, Meluleni G, Coleman F, Goldberg J, Pier G . Protection against fatal Pseudomonas aeruginosa pneumonia in mice after nasal immunization with a live, attenuated aroA deletion mutant. Infect Immun. 2003; 71(3):1453-61. PMC: 148856. DOI: 10.1128/IAI.71.3.1453-1461.2003. View

17.

Garau J, Gomez L . Pseudomonas aeruginosa pneumonia. Curr Opin Infect Dis. 2003; 16(2):135-43. DOI: 10.1097/00001432-200304000-00010. View

18.

Bystrova O, Lindner B, Moll H, Kocharova N, Knirel Y, Zahringer U . Structure of the lipopolysaccharide of Pseudomonas aeruginosa O-12 with a randomly O-acetylated core region. Carbohydr Res. 2003; 338(18):1895-905. DOI: 10.1016/s0008-6215(03)00290-8. View

19.

Bystrova O, Shashkov A, Kocharova N, Knirel Y, Zahringer U, Pier G . Elucidation of the structure of the lipopolysaccharide core and the linkage between the core and the O-antigen in Pseudomonas aeruginosa immunotype 5 using strong alkaline degradation of the lipopolysaccharide. Biochemistry (Mosc). 2003; 68(8):918-25. DOI: 10.1023/a:1025759217501. View

20.

Tsui I, Yip C, Hackett J, Morris C . The type IVB pili of Salmonella enterica serovar Typhi bind to the cystic fibrosis transmembrane conductance regulator. Infect Immun. 2003; 71(10):6049-50. PMC: 201034. DOI: 10.1128/IAI.71.10.6049-6050.2003. View