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Science 19 November 1999:
Vol. 286. no. 5444, pp. 1561 - 1565
DOI: 10.1126/science.286.5444.1561
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Reports

Specific Lipopolysaccharide Found in Cystic Fibrosis Airway Pseudomonas aeruginosa

Robert K. Ernst, 1 Eugene C. Yi, 2 Lin Guo, 1* Kheng B. Lim, 2dagger Jane L. Burns, 3 Murray Hackett, 2 Samuel I. Miller 1ddagger

Cystic fibrosis (CF) patients develop chronic airway infections with Pseudomonas aeruginosa (PA). Pseudomonas aeruginosa synthesized lipopolysaccharide (LPS) with a variety of penta- and hexa-acylated lipid A structures under different environmental conditions. CF patient PA synthesized LPS with specific lipid A structures indicating unique recognition of the CF airway environment. CF-specific lipid A forms containing palmitate and aminoarabinose were associated with resistance to cationic antimicrobial peptides and increased inflammatory responses, indicating that they are likely to be involved in airway disease.

1 Departments of Medicine and Microbiology,
2 Department of Medicinal Chemistry,
3 Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
*   Present address: Immunex Corporation, 51 University Street, Seattle, WA 98101, USA.

dagger    Present address: Bristol-Myers Squibb, Pharmaceutical Research Institute, Post Office Box 4000, Princeton, NJ 08543, USA.

ddagger    To whom correspondence should be addressed. E-mail: millersi{at}u.washington.edu

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   Abstract »    Full Text »    PDF »
Airway surface pH in subjects with cystic fibrosis.
D. McShane, J.C. Davies, M.G. Davies, A. Bush, D.M. Geddes, and E.W.F.W. Alton (2003)
Eur. Respir. J. 21, 37-42
   Abstract »    Full Text »    PDF »
Solution structure and dynamics of the outer membrane enzyme PagP by NMR.
P. M. Hwang, W.-Y. Choy, E. I. Lo, L. Chen, J. D. Forman-Kay, C. R. H. Raetz, G. G. Prive, R. E. Bishop, and L. E. Kay (2002)
PNAS 99, 13560-13565
   Abstract »    Full Text »    PDF »
Susceptibility of Nontypeable Haemophilus influenzae to Human {beta}-Defensins Is Influenced by Lipooligosaccharide Acylation.
T. D. Starner, W. E. Swords, M. A. Apicella, and P. B. McCray Jr. (2002)
Infect. Immun. 70, 5287-5289
   Abstract »    Full Text »    PDF »
mig-14 Is a Salmonella Gene That Plays a Role in Bacterial Resistance to Antimicrobial Peptides.
I. E. Brodsky, R. K. Ernst, S. I. Miller, and S. Falkow (2002)
J. Bacteriol. 184, 3203-3213
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa cells adapted to benzalkonium chloride show resistance to other membrane-active agents but not to clinically relevant antibiotics.
M. F. Loughlin, M. V. Jones, and P. A. Lambert (2002)
J. Antimicrob. Chemother. 49, 631-639
   Abstract »    Full Text »    PDF »
Pseudomonas aeruginosa Quorum-Sensing Systems May Control Virulence Factor Expression in the Lungs of Patients with Cystic Fibrosis.
D. L. Erickson, R. Endersby, A. Kirkham, K. Stuber, D. D. Vollman, H. R. Rabin, I. Mitchell, and D. G. Storey (2002)
Infect. Immun. 70, 1783-1790
   Abstract »    Full Text »    PDF »
Endotoxin Activity and Inflammatory Markers in the Airways of Young Patients with Cystic Fibrosis.
M. S. Muhlebach and T. L. Noah (2002)
Am. J. Respir. Crit. Care Med. 165, 911-915
   Abstract »    Full Text »    PDF »
Detection of simple mutations and polymorphisms in large genomic regions.
E. V. Sokurenko, V. Tchesnokova, A. T. Yeung, C. A. Oleykowski, E. Trintchina, K. T. Hughes, R. A. Rashid, J. M. Brint, S. L. Moseley, and S. Lory (2001)
Nucleic Acids Res. 29, e111
   Abstract »    Full Text »    PDF »
Cathelicidin Peptides Inhibit Multiply Antibiotic-Resistant Pathogens from Patients with Cystic Fibrosis.
L. Saiman, S. Tabibi, T. D. Starner, P. San Gabriel, P. L. Winokur, H. P. Jia, P. B. McCray Jr., and B. F. Tack (2001)
Antimicrob. Agents Chemother. 45, 2838-2844
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Protein secretion and the pathogenesis of bacterial infections.
V. T. Lee and O. Schneewind (2001)
Genes & Dev. 15, 1725-1752
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Identification of Proteus mirabilis Mutants with Increased Sensitivity to Antimicrobial Peptides.
A. J. McCoy, H. Liu, T. J. Falla, and J. S. Gunn (2001)
Antimicrob. Agents Chemother. 45, 2030-2037
   Abstract »    Full Text »    PDF »
Identification of Legionella pneumophila rcp, a pagP-Like Gene That Confers Resistance to Cationic Antimicrobial Peptides and Promotes Intracellular Infection.
M. Robey, W. O'Connell, and N. P. Cianciotto (2001)
Infect. Immun. 69, 4276-4286
   Abstract »    Full Text »    PDF »
Invited review: Bacterial lipopolysaccharides and innate immunity.
C. Alexander and E. Th. Rietschel (2001)
Innate Immunity 7, 167-202
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The Pleiotropic Two-Component Regulatory System PhoP-PhoQ.
E. A. Groisman (2001)
J. Bacteriol. 183, 1835-1842
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Bacterial modification of LPS and resistance to antimicrobial peptides.
J. S. Gunn (2001)
Innate Immunity 7, 57-62
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Regulated covalent modifications of lipid A.
C. R.H. Raetz (2001)
Innate Immunity 7, 73-78
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Genetic and Functional Analysis of a PmrA-PmrB-Regulated Locus Necessary for Lipopolysaccharide Modification, Antimicrobial Peptide Resistance, and Oral Virulence of Salmonella enterica Serovar Typhimurium.
J. S. Gunn, S. S. Ryan, J. C. Van Velkinburgh, R. K. Ernst, and S. I. Miller (2000)
Infect. Immun. 68, 6139-6146
   Abstract »    Full Text »    PDF »
Comparison of proteins expressed by Pseudomonas aeruginosa strains representing initial and chronic isolates from a cystic fibrosis patient: an analysis by 2-D gel electrophoresis and capillary column liquid chromatography-tandem mass spectrometry.
S. L. Hanna, N. E. Sherman, M. T. Kinter, and J. B. Goldberg (2000)
Microbiology 146, 2495-2508
   Abstract »    Full Text »


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