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Clin Microbiol Rev. Apr 1991; 4(2): 191–206.
PMCID: PMC358191

Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients.

Abstract

Pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa is the leading cause of mortality among patients suffering from cystic fibrosis. Alginate-producing P. aeruginosa is uniquely associated with the environment of the cystic fibrosis-affected lung, where alginate is believed to increase resistance to both the host immune system and antibiotic therapy. Recent evidence indicates that P. aeruginosa is most resistant to antibiotics when the infecting cells are present as a biofilm, as they appear to be in the lungs of cystic fibrosis patients. Inhibition of the protective alginate barrier with nontoxic compounds targeted against alginate biosynthetic and regulatory proteins may prove useful in eradicating P. aeruginosa from this environment. Our research has dealt with elucidating the biosynthetic pathway and regulatory mechanism(s) responsible for alginate synthesis by P. aeruginosa. This review summarizes reports on the role of alginate in cystic fibrosis-associated pulmonary infections caused by P. aeruginosa and provides details about the biosynthesis and regulation of this exopolysaccharide.

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  • Baltimore RS, Mitchell M. Immunologic investigations of mucoid strains of Pseudomonas aeruginosa: comparison of susceptibility to opsonic antibody in mucoid and nonmucoid strains. J Infect Dis. 1980 Feb;141(2):238–247. [PubMed]
  • Banerjee PC, Vanags RI, Chakrabarty AM, Maitra PK. Alginic acid synthesis in Pseudomonas aeruginosa mutants defective in carbohydrate metabolism. J Bacteriol. 1983 Jul;155(1):238–245. [PMC free article] [PubMed]
  • Banerjee PC, Vanags RI, Chakrabarty AM, Maitra PK. Fructose 1,6-bisphosphate aldolase activity is essential for synthesis of alginate from glucose by Pseudomonas aeruginosa. J Bacteriol. 1985 Jan;161(1):458–460. [PMC free article] [PubMed]
  • Baxter PS, Goldhill J, Hardcastle J, Hardcastle PT, Taylor CJ. Accounting for cystic fibrosis. Nature. 1988 Sep 15;335(6187):211–211. [PubMed]
  • Behm JK, Hagiwara G, Lewiston NJ, Quinton PM, Wine JJ. Hyposecretion of beta-adrenergically induced sweating in cystic fibrosis heterozygotes. Pediatr Res. 1987 Sep;22(3):271–276. [PubMed]
  • Bender JG, Florman AL, Van Epps DE. Correlation of serum opsonic activity in cystic fibrosis with colonization and disease state: measurement of opsonins to Pseudomonas aeruginosa by neutrophil superoxide anion generation. Pediatr Res. 1987 Oct;22(4):383–388. [PubMed]
  • Bergan T, Hoiby N. Epidemiological markers for Pseudomonas aeruginosa. 6. Relationship between concomitant non-mucoid and mucoid strains from the respiratory tract in cystic fibrosis. Acta Pathol Microbiol Scand Suppl. 1975 Dec;83(6):553–560. [PubMed]
  • Berry A, DeVault JD, Chakrabarty AM. High osmolarity is a signal for enhanced algD transcription in mucoid and nonmucoid Pseudomonas aeruginosa strains. J Bacteriol. 1989 May;171(5):2312–2317. [PMC free article] [PubMed]
  • Blackwood LL, Pennington JE. Influence of mucoid coating on clearance of Pseudomonas aeruginosa from lungs. Infect Immun. 1981 May;32(2):443–448. [PMC free article] [PubMed]
  • Boyce JR, Miller RV. Selection of nonmucoid derivatives of mucoid Pseudomonas aeruginosa is strongly influenced by the level of iron in the culture medium. Infect Immun. 1982 Aug;37(2):695–701. [PMC free article] [PubMed]
  • Burns MW, May JR. Bacterial precipitins in serum of patients with cystic fibrosis. Lancet. 1968 Feb 10;1(7537):270–272. [PubMed]
  • Cabral DA, Loh BA, Speert DP. Mucoid Pseudomonas aeruginosa resists nonopsonic phagocytosis by human neutrophils and macrophages. Pediatr Res. 1987 Oct;22(4):429–431. [PubMed]
  • Carlson DM, Matthews LW. Polyuronic acids produced by Pseudomonas aeruginosa. Biochemistry. 1966 Sep;5(9):2817–2822. [PubMed]
  • CETIN ET, TOERECI K, ANG O. ENCAPSULATED PSEUDOMONAS AERUGINOSA (PSEUDOMONAS AERUGINOSA MUCOSUS) STRAINS. J Bacteriol. 1965 May;89:1432–1433. [PMC free article] [PubMed]
  • Chan R, Lam JS, Lam K, Costerton JW. Influence of culture conditions on expression of the mucoid mode of growth of Pseudomonas aeruginosa. J Clin Microbiol. 1984 Jan;19(1):8–16. [PMC free article] [PubMed]
  • Chitnis CE, Ohman DE. Cloning of Pseudomonas aeruginosa algG, which controls alginate structure. J Bacteriol. 1990 Jun;172(6):2894–2900. [PMC free article] [PubMed]
  • Coburn J, Dillon ST, Iglewski BH, Gill DM. Exoenzyme S of Pseudomonas aeruginosa ADP-ribosylates the intermediate filament protein vimentin. Infect Immun. 1989 Mar;57(3):996–998. [PMC free article] [PubMed]
  • Coburn J, Wyatt RT, Iglewski BH, Gill DM. Several GTP-binding proteins, including p21c-H-ras, are preferred substrates of Pseudomonas aeruginosa exoenzyme S. J Biol Chem. 1989 May 25;264(15):9004–9008. [PubMed]
  • Darzins A, Chakrabarty AM. Cloning of genes controlling alginate biosynthesis from a mucoid cystic fibrosis isolate of Pseudomonas aeruginosa. J Bacteriol. 1984 Jul;159(1):9–18. [PMC free article] [PubMed]
  • Darzins A, Frantz B, Vanags RI, Chakrabarty AM. Nucleotide sequence analysis of the phosphomannose isomerase gene (pmi) of Pseudomonas aeruginosa and comparison with the corresponding Escherichia coli gene manA. Gene. 1986;42(3):293–302. [PubMed]
  • Darzins A, Nixon LL, Vanags RI, Chakrabarty AM. Cloning of Escherichia coli and Pseudomonas aeruginosa phosphomannose isomerase genes and their expression in alginate-negative mutants of Pseudomonas aeruginosa. J Bacteriol. 1985 Jan;161(1):249–257. [PMC free article] [PubMed]
  • Darzins A, Wang SK, Vanags RI, Chakrabarty AM. Clustering of mutations affecting alginic acid biosynthesis in mucoid Pseudomonas aeruginosa. J Bacteriol. 1985 Nov;164(2):516–524. [PMC free article] [PubMed]
  • Davis PB, di Sant'Agnese PA. A review. Cystic fibrosis at forty--quo vadis? Pediatr Res. 1980 Feb;14(2):83–87. [PubMed]
  • Deretic V, Dikshit R, Konyecsni WM, Chakrabarty AM, Misra TK. The algR gene, which regulates mucoidy in Pseudomonas aeruginosa, belongs to a class of environmentally responsive genes. J Bacteriol. 1989 Mar;171(3):1278–1283. [PMC free article] [PubMed]
  • Deretic V, Gill JF, Chakrabarty AM. Gene algD coding for GDPmannose dehydrogenase is transcriptionally activated in mucoid Pseudomonas aeruginosa. J Bacteriol. 1987 Jan;169(1):351–358. [PMC free article] [PubMed]
  • Deretic V, Gill JF, Chakrabarty AM. Pseudomonas aeruginosa infection in cystic fibrosis: nucleotide sequence and transcriptional regulation of the algD gene. Nucleic Acids Res. 1987 Jun 11;15(11):4567–4581. [PMC free article] [PubMed]
  • Deretic V, Tomasek P, Darzins A, Chakrabarty AM. Gene amplification induces mucoid phenotype in rec-2 Pseudomonas aeruginosa exposed to kanamycin. J Bacteriol. 1986 Feb;165(2):510–516. [PMC free article] [PubMed]
  • DeVault JD, Kimbara K, Chakrabarty AM. Pulmonary dehydration and infection in cystic fibrosis: evidence that ethanol activates alginate gene expression and induction of mucoidy in Pseudomonas aeruginosa. Mol Microbiol. 1990 May;4(5):737–745. [PubMed]
  • Diaz E, Mosovich LL, Neter E. Serogroups of Pseudomonas aeruginosa and the immune response of patients with cystic fibrosis. J Infect Dis. 1970 Mar;121(3):269–274. [PubMed]
  • DI SANT'AGNESE PA, DARLING RC, PERERA GA, SHEA E. Sweat electrolyte disturbances associated with childhood pancreatic disease. Am J Med. 1953 Dec;15(6):777–784. [PubMed]
  • di Sant'Agnese PA, Davis PB. Research in cystic fibrosis (third of three parts). N Engl J Med. 1976 Sep 9;295(11):597–602. [PubMed]
  • di Sant'agnese PA, Davis PB. Cystic fibrosis in adults. 75 cases and a review of 232 cases in the literature. Am J Med. 1979 Jan;66(1):121–132. [PubMed]
  • Doggett RG. Incidence of mucoid Pseudomonas aeruginosa from clinical sources. Appl Microbiol. 1969 Nov;18(5):936–937. [PMC free article] [PubMed]
  • Doggett RG, Harrison GM. Pseudomonas aeruginosa: immune status in patients with cystic fibrosis. Infect Immun. 1972 Oct;6(4):628–635. [PMC free article] [PubMed]
  • Doggett RG, Harrison GM, Carter RE. Mucoid Pseudomonas aeruginosa in patients with chronic illnesses. Lancet. 1971 Jan 30;1(7692):236–237. [PubMed]
  • DOGGETT RG, HARRISON GM, WALLIS ES. COMPARISON OF SOME PROPERTIES OF PSEUDOMONAS AERUGINOSA ISOLATED FROM INFECTIONS IN PERSONS WITH AND WITHOUT CYSTIC FIBROSIS. J Bacteriol. 1964 Feb;87:427–431. [PMC free article] [PubMed]
  • Doig P, Smith NR, Todd T, Irvin RT. Characterization of the binding of Pseudomonas aeruginosa alginate to human epithelial cells. Infect Immun. 1987 Jun;55(6):1517–1522. [PMC free article] [PubMed]
  • Dorin JR, Novak M, Hill RE, Brock DJ, Secher DS, van Heyningen V. A clue to the basic defect in cystic fibrosis from cloning the CF antigen gene. Nature. 1987 Apr 9;326(6113):614–617. [PubMed]
  • Dunne WM, Jr, Buckmire FL. Partial purification and characterization of a polymannuronic acid depolymerase produced by a mucoid strain of Pseudomonas aeruginosa isolated from a patient with cystic fibrosis. Appl Environ Microbiol. 1985 Sep;50(3):562–567. [PMC free article] [PubMed]
  • Eftekhar F, Speert DP. Alginase treatment of mucoid Pseudomonas aeruginosa enhances phagocytosis by human monocyte-derived macrophages. Infect Immun. 1988 Nov;56(11):2788–2793. [PMC free article] [PubMed]
  • Evans LR, Linker A. Production and characterization of the slime polysaccharide of Pseudomonas aeruginosa. J Bacteriol. 1973 Nov;116(2):915–924. [PMC free article] [PubMed]
  • Fialho AM, Zielinski NA, Fett WF, Chakrabarty AM, Berry A. Distribution of alginate gene sequences in the Pseudomonas rRNA homology group I-Azomonas-Azotobacter lineage of superfamily B procaryotes. Appl Environ Microbiol. 1990 Feb;56(2):436–443. [PMC free article] [PubMed]
  • Flynn JL, Ohman DE. Cloning of genes from mucoid Pseudomonas aeruginosa which control spontaneous conversion to the alginate production phenotype. J Bacteriol. 1988 Apr;170(4):1452–1460. [PMC free article] [PubMed]
  • Flynn JL, Ohman DE. Use of a gene replacement cosmid vector for cloning alginate conversion genes from mucoid and nonmucoid Pseudomonas aeruginosa strains: algS controls expression of algT. J Bacteriol. 1988 Jul;170(7):3228–3236. [PMC free article] [PubMed]
  • Frizzell RA, Rechkemmer G, Shoemaker RL. Altered regulation of airway epithelial cell chloride channels in cystic fibrosis. Science. 1986 Aug 1;233(4763):558–560. [PubMed]
  • Fyfe JA, Govan JR. Alginate synthesis in mucoid Pseudomonas aeruginosa: a chromosomal locus involved in control. J Gen Microbiol. 1980 Aug;119(2):443–450. [PubMed]
  • Gill JF, Deretic V, Chakrabarty AM. Overproduction and assay of Pseudomonas aeruginosa phosphomannose isomerase. J Bacteriol. 1986 Aug;167(2):611–615. [PMC free article] [PubMed]
  • Goldberg JB, Ohman DE. Construction and characterization of Pseudomonas aeruginosa algB mutants: role of algB in high-level production of alginate. J Bacteriol. 1987 Apr;169(4):1593–1602. [PMC free article] [PubMed]
  • Gordon CA, Hodges NA, Marriott C. Antibiotic interaction and diffusion through alginate and exopolysaccharide of cystic fibrosis-derived Pseudomonas aeruginosa. J Antimicrob Chemother. 1988 Nov;22(5):667–674. [PubMed]
  • Govan JR. Mucoid strains of Pseudomonas aeruginosa: the influence of culture medium on the stability of mucus production. J Med Microbiol. 1975 Nov;8(4):513–522. [PubMed]
  • Govan JR, Fyfe JA. Mucoid Pseudomonas aeruginosa and cystic fibrosis: resistance of the mucoid from to carbenicillin, flucloxacillin and tobramycin and the isolation of mucoid variants in vitro. J Antimicrob Chemother. 1978 May;4(3):233–240. [PubMed]
  • Govan JR, Fyfe JA, Jarman TR. Isolation of alginate-producing mutants of Pseudomonas fluorescens, Pseudomonas putida and Pseudomonas mendocina. J Gen Microbiol. 1981 Jul;125(1):217–220. [PubMed]
  • Govan JR, Harris GS. Pseudomonas aeruginosa and cystic fibrosis: unusual bacterial adaptation and pathogenesis. Microbiol Sci. 1986 Oct;3(10):302–308. [PubMed]
  • Hancock RE, Mutharia LM, Chan L, Darveau RP, Speert DP, Pier GB. Pseudomonas aeruginosa isolates from patients with cystic fibrosis: a class of serum-sensitive, nontypable strains deficient in lipopolysaccharide O side chains. Infect Immun. 1983 Oct;42(1):170–177. [PMC free article] [PubMed]
  • Hansson GC. Cystic fibrosis and chloride-secreting diarrhoea. Nature. 1988 Jun 23;333(6175):711–711. [PubMed]
  • Haug A, Larsen B. Biosynthesis of alginate. II. Polymannuronic acid C-5-epimerase from Azotobacter vinelandii (Lipman). Carbohydr Res. 1971 Apr;17(2):297–308. [PubMed]
  • Hoiby N, Axelsen NH. Identification and quantitation of precipitins against Pseudomonas aeruginosa in patients with cystic fibrosis by means of crossed immunoelectrophoresis with intermediate gel. Acta Pathol Microbiol Scand B Microbiol Immunol. 1973 Jun;81(3):298–308. [PubMed]
  • HUANG NN, VAN LOON EL, SHENG KT. The flora of the respiratory tract of patients with cystic fibrosis of the pancreas. J Pediatr. 1961 Oct;59:512–521. [PubMed]
  • Hulton CS, Seirafi A, Hinton JC, Sidebotham JM, Waddell L, Pavitt GD, Owen-Hughes T, Spassky A, Buc H, Higgins CF. Histone-like protein H1 (H-NS), DNA supercoiling, and gene expression in bacteria. Cell. 1990 Nov 2;63(3):631–642. [PubMed]
  • IACOCCA VF, SIBINGA M, BARBERO GJ. RESPIRATORY TRACT BACTERIOLOGY IN CYSTIC FIBROSIS. Am J Dis Child. 1963 Sep;106:315–324. [PubMed]
  • Kato J, Chu L, Kitano K, DeVault JD, Kimbara K, Chakrabarty AM, Misra TK. Nucleotide sequence of a regulatory region controlling alginate synthesis in Pseudomonas aeruginosa: characterization of the algR2 gene. Gene. 1989 Dec 7;84(1):31–38. [PubMed]
  • Kato J, Misra TK, Chakrabarty AM. AlgR3, a protein resembling eukaryotic histone H1, regulates alginate synthesis in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A. 1990 Apr;87(8):2887–2891. [PMC free article] [PubMed]
  • Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC. Identification of the cystic fibrosis gene: genetic analysis. Science. 1989 Sep 8;245(4922):1073–1080. [PubMed]
  • Kimbara K, Chakrabarty AM. Control of alginate synthesis in Pseudomonas aeruginosa: regulation of the algR1 gene. Biochem Biophys Res Commun. 1989 Oct 31;164(2):601–608. [PubMed]
  • Klinger JD, Straus DC, Hilton CB, Bass JA. Antibodies to proteases and exotoxin A of Pseudomonas aeruginosa in patients with cystic fibrosis: Demonstration by radioimmunoassay. J Infect Dis. 1978 Jul;138(1):49–48. [PubMed]
  • Knowles M, Gatzy J, Boucher R. Relative ion permeability of normal and cystic fibrosis nasal epithelium. J Clin Invest. 1983 May;71(5):1410–1417. [PMC free article] [PubMed]
  • Knowles MR, Stutts MJ, Spock A, Fischer N, Gatzy JT, Boucher RC. Abnormal ion permeation through cystic fibrosis respiratory epithelium. Science. 1983 Sep 9;221(4615):1067–1070. [PubMed]
  • Konyecsni WM, Deretic V. DNA sequence and expression analysis of algP and algQ, components of the multigene system transcriptionally regulating mucoidy in Pseudomonas aeruginosa: algP contains multiple direct repeats. J Bacteriol. 1990 May;172(5):2511–2520. [PMC free article] [PubMed]
  • Krieg DP, Helmke RJ, German VF, Mangos JA. Resistance of mucoid Pseudomonas aeruginosa to nonopsonic phagocytosis by alveolar macrophages in vitro. Infect Immun. 1988 Dec;56(12):3173–3179. [PMC free article] [PubMed]
  • Kulczycki LL, Schauf V. Cystic fibrosis in blacks in Washington, DC: incidence and characteristics. Am J Dis Child. 1974 Jan;127(1):64–67. [PubMed]
  • Lam J, Chan R, Lam K, Costerton JW. Production of mucoid microcolonies by Pseudomonas aeruginosa within infected lungs in cystic fibrosis. Infect Immun. 1980 May;28(2):546–556. [PMC free article] [PubMed]
  • Larsen B, Haug A. Biosynthesis of alginate. 1. Composition and structure of alginate produced by Azotobacter vinelandii (Lipman). Carbohydr Res. 1971 Apr;17(2):287–296. [PubMed]
  • Larsen B, Haug A. Biosynthesis of alginate. 3. Tritium incorporation with polymannuronic acid 5-epimerase from Azotobacter vinelandii. Carbohydr Res. 1971 Dec;20(2):225–232. [PubMed]
  • Li M, McCann JD, Liedtke CM, Nairn AC, Greengard P, Welsh MJ. Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium. Nature. 1988 Jan 28;331(6154):358–360. [PubMed]
  • Lin TY, Hassid WZ. Isolation of guanosine diphosphate uronic acids from a marine brown alga, Fucus gardneri Silva. J Biol Chem. 1966 Jul 25;241(14):3283–3293. [PubMed]
  • Lin TY, Hassid WZ. Pathway of algnic acid synthesis in the marine brown alga, Fucus gardneri Silva. J Biol Chem. 1966 Nov 25;241(22):5284–5297. [PubMed]
  • LINKER A, JONES RS. A POLYSACCHARIDE RESEMBLING ALGINIC ACID FROM A PSEUDOMONAS MICRO-ORGANISM. Nature. 1964 Oct 10;204:187–188. [PubMed]
  • Linker A, Jones RS. A new polysaccharide resembling alginic acid isolated from pseudomonads. J Biol Chem. 1966 Aug 25;241(16):3845–3851. [PubMed]
  • Liu PV. Extracellular toxins of Pseudomonas aeruginosa. J Infect Dis. 1974 Nov;130 (Suppl)(0):S94–S99. [PubMed]
  • Lynn AR, Sokatch JR. Incorporation of isotope from specifically labeled glucose into alginates of Pseudomonas aeruginosa and Azotobacter vinelandii. J Bacteriol. 1984 Jun;158(3):1161–1162. [PMC free article] [PubMed]
  • Mangos JA. Microperfusion study of the sweat gland abnormality in cystic fibrosis. Tex Rep Biol Med. 1973 Winter;31(4):651–663. [PubMed]
  • Marrie TJ, Harding GK, Ronald AR, Dikkema J, Lam J, Hoban S, Costerton JW. Influence of mucoidy on antibody coating of Pseudomonas aeruginosa. J Infect Dis. 1979 Mar;139(3):357–361. [PubMed]
  • Martin DR. Mucoid variation in Pseudomonas aeruginosa induced by the action of phage. J Med Microbiol. 1973 Feb;6(1):111–118. [PubMed]
  • McPherson MA, Dormer RL. The molecular and biochemical basis of cystic fibrosis. Biosci Rep. 1987 Mar;7(3):167–185. [PubMed]
  • McPherson MA, Goodchild MC. The biochemical defect in cystic fibrosis. Clin Sci (Lond) 1988 Apr;74(4):337–345. [PubMed]
  • Meshulam T, Verbrugh HA, Verhoef J. Opsonization and phagocytosis of mucoid and non-mucoid Pseudomonas aeruginosa strains. Eur J Clin Microbiol. 1982 Apr;1(2):112–117. [PubMed]
  • Mohr CD, Martin DW, Konyecsni WM, Govan JR, Lory S, Deretic V. Role of the far-upstream sites of the algD promoter and the algR and rpoN genes in environmental modulation of mucoidy in Pseudomonas aeruginosa. J Bacteriol. 1990 Nov;172(11):6576–6580. [PMC free article] [PubMed]
  • Nicas TI, Iglewski BH. The contribution of exoproducts to virulence of Pseudomonas aeruginosa. Can J Microbiol. 1985 Apr;31(4):387–392. [PubMed]
  • Nichols WW, Evans MJ, Slack MP, Walmsley HL. The penetration of antibiotics into aggregates of mucoid and non-mucoid Pseudomonas aeruginosa. J Gen Microbiol. 1989 May;135(5):1291–1303. [PubMed]
  • Ogle JW, Janda JM, Woods DE, Vasil ML. Characterization and use of a DNA probe as an epidemiological marker for Pseudomonas aeruginosa. J Infect Dis. 1987 Jan;155(1):119–126. [PubMed]
  • Ohman DE, Chakrabarty AM. Utilization of human respiratory secretions by mucoid Pseudomonas aeruginosa of cystic fibrosis origin. Infect Immun. 1982 Aug;37(2):662–669. [PMC free article] [PubMed]
  • Ohman DE, West MA, Flynn JL, Goldberg JB. Method for gene replacement in Pseudomonas aeruginosa used in construction of recA mutants: recA-independent instability of alginate production. J Bacteriol. 1985 Jun;162(3):1068–1074. [PMC free article] [PubMed]
  • Oliver AM, Weir DM. Inhibition of bacterial binding to mouse macrophages by Pseudomonas alginate. J Clin Lab Immunol. 1983 Apr;10(4):221–224. [PubMed]
  • Ombaka EA, Cozens RM, Brown MR. Influence of nutrient limitation of growth on stability and production of virulence factors of mucoid and nonmucoid strains of Pseudomonas aeruginosa. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S880–S888. [PubMed]
  • Pier GB, Small GJ, Warren HB. Protection against mucoid Pseudomonas aeruginosa in rodent models of endobronchial infections. Science. 1990 Aug 3;249(4968):537–540. [PubMed]
  • Pindar DF, Bucke C. The biosynthesis of alginic acid by Azotobacter vinelandii. Biochem J. 1975 Dec;152(3):617–622. [PMC free article] [PubMed]
  • Pugashetti BK, Vadas L, Prihar HS, Feingold DS. GDPmannose dehydrogenase and biosynthesis of alginate-like polysaccharide in a mucoid strain of Pseudomonas aeruginosa. J Bacteriol. 1983 Feb;153(2):1107–1110. [PMC free article] [PubMed]
  • Quinton PM. Chloride impermeability in cystic fibrosis. Nature. 1983 Feb 3;301(5899):421–422. [PubMed]
  • Ramphal R, Pier GB. Role of Pseudomonas aeruginosa mucoid exopolysaccharide in adherence to tracheal cells. Infect Immun. 1985 Jan;47(1):1–4. [PMC free article] [PubMed]
  • Reynolds HY, Kazmierowski JA, Newball HH. Specificity of opsonic antibodies to enhance phagocytosis of Pseudomonas aeruginosa by human alveolar macrophages. J Clin Invest. 1975 Aug;56(2):376–385. [PMC free article] [PubMed]
  • Pseudomonas aeruginosa infections: persisting problems and current research to find new therapies. Ann Intern Med. 1975 Jun;82(6):819–831. [PubMed]
  • Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989 Sep 8;245(4922):1066–1073. [PubMed]
  • Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989 Sep 8;245(4922):1059–1065. [PubMed]
  • Ronson CW, Nixon BT, Ausubel FM. Conserved domains in bacterial regulatory proteins that respond to environmental stimuli. Cell. 1987 Jun 5;49(5):579–581. [PubMed]
  • Roychoudhury S, May TB, Gill JF, Singh SK, Feingold DS, Chakrabarty AM. Purification and characterization of guanosine diphospho-D-mannose dehydrogenase. A key enzyme in the biosynthesis of alginate by Pseudomonas aeruginosa. J Biol Chem. 1989 Jun 5;264(16):9380–9385. [PubMed]
  • Ruhen RW, Holt PG, Papadimitriou JM. Antiphagocytic effect of Pseudomonas aeruginosa exopolysaccharide. J Clin Pathol. 1980 Dec;33(12):1221–1222. [PMC free article] [PubMed]
  • Russell NJ, Gacesa P. Chemistry and biology of the alginate of mucoid strains of Pseudomonas aeruginosa in cystic fibrosis. Mol Aspects Med. 1988;10(1):1–91. [PubMed]
  • Sasse-Dwight S, Gralla JD. Role of eukaryotic-type functional domains found in the prokaryotic enhancer receptor factor sigma 54. Cell. 1990 Sep 7;62(5):945–954. [PubMed]
  • Sato K, Sato F. Defective beta adrenergic response of cystic fibrosis sweat glands in vivo and in vitro. J Clin Invest. 1984 Jun;73(6):1763–1771. [PMC free article] [PubMed]
  • Schoumacher RA, Shoemaker RL, Halm DR, Tallant EA, Wallace RW, Frizzell RA. Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells. Nature. 1987 Dec 24;330(6150):752–754. [PubMed]
  • Schulz IJ. Micropuncture studies of the sweat formation in cystic fibrosis patients. J Clin Invest. 1969 Aug;48(8):1470–1477. [PMC free article] [PubMed]
  • Schwarzmann S, Boring JR. Antiphagocytic Effect of Slime from a Mucoid Strain of Pseudomonas aeruginosa. Infect Immun. 1971 Jun;3(6):762–767. [PMC free article] [PubMed]
  • Sherbrock-Cox V, Russell NJ, Gacesa P. The purification and chemical characterisation of the alginate present in extracellular material produced by mucoid strains of Pseudomonas aeruginosa. Carbohydr Res. 1984 Dec 15;135(1):147–154. [PubMed]
  • Skjåk-Braek G, Grasdalen H, Larsen B. Monomer sequence and acetylation pattern in some bacterial alginates. Carbohydr Res. 1986 Oct 15;154:239–250. [PubMed]
  • Slack MP, Nichols WW. The penetration of antibiotics through sodium alginate and through the exopolysaccharide of a mucoid strain of Pseudomonas aeruginosa. Lancet. 1981 Sep 5;2(8245):502–503. [PubMed]
  • Speert DP. Host defenses in patients with cystic fibrosis: modulation by Pseudomonas aeruginosa. Surv Synth Pathol Res. 1985;4(1):14–33. [PubMed]
  • Thomassen MJ, Demko CA, Boxerbaum B, Stern RC, Kuchenbrod PJ. Multiple of isolates of Pseudomonas aeruginosa with differing antimicrobial susceptibility patterns from patients with cystic fibrosis. J Infect Dis. 1979 Dec;140(6):873–880. [PubMed]
  • Vasil ML. Pseudomonas aeruginosa: biology, mechanisms of virulence, epidemiology. J Pediatr. 1986 May;108(5 Pt 2):800–805. [PubMed]
  • Wallwork JC, Brenchley P, McCarthy J, Allan JD, Moss D, Ward AM, Holzel A, Williams RF, McFarlane H. Some aspects of immunity in patients with cystic fibrosis. Clin Exp Immunol. 1974 Nov;18(3):303–320. [PMC free article] [PubMed]
  • Wang SK, Sa'-Correia I, Darzins A, Chakrabarty AM. Characterization of the Pseudomonas aeruginosa alginate (alg) gene region II. J Gen Microbiol. 1987 Aug;133(8):2303–2314. [PubMed]
  • Welsh MJ, Liedtke CM. Chloride and potassium channels in cystic fibrosis airway epithelia. Nature. 322(6078):467–470. [PubMed]
  • White MB, Amos J, Hsu JM, Gerrard B, Finn P, Dean M. A frame-shift mutation in the cystic fibrosis gene. Nature. 1990 Apr 12;344(6267):665–667. [PubMed]
  • White R, Woodward S, Leppert M, O'Connell P, Hoff M, Herbst J, Lalouel JM, Dean M, Vande Woude G. A closely linked genetic marker for cystic fibrosis. Nature. 318(6044):382–384. [PubMed]
  • Williams RJ, Govan JR. Pyocine typing of mucoid strains of Pseudomonas aeruginosa isolated from children with cystic fibrosis. J Med Microbiol. 1973 Aug;6(3):409–412. [PubMed]
  • Wilson R, Roberts D, Cole P. Effect of bacterial products on human ciliary function in vitro. Thorax. 1985 Feb;40(2):125–131. [PMC free article] [PubMed]
  • Wood RE, Boat TF, Doershuk CF. Cystic fibrosis. Am Rev Respir Dis. 1976 Jun;113(6):833–878. [PubMed]
  • Woods DE, Bass JA, Johanson WG, Jr, Straus DC. Role of adherence in the pathogenesis of Pseudomonas aeruginosa lung infection in cystic fibrosis patients. Infect Immun. 1980 Dec;30(3):694–699. [PMC free article] [PubMed]
  • Zierdt CH, Schmidt PJ. Dissociation in Pseudomonas aeruginosa. J Bacteriol. 1964 May;87(5):1003–1010. [PMC free article] [PubMed]

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