Role of mutant CFTR in hypersusceptibility of cystic fibrosis patients to lung infections

Science

Volumn 271, Issue 5245, 1996, Pages 64-67

  Pier, Gerald B ^a   Grout, Martha ^a   Zaidi, Tanweer S ^a   Olsen, John C ^b   Johnson, Larry G ^b   Yankaskas, James R ^b   Goldberg, Joanna B ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIUM LIPOPOLYSACCHARIDE; MUTANT PROTEIN; OLIGOSACCHARIDE; TRANSMEMBRANE CONDUCTANCE REGULATOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BACTERIAL INFECTION; CONTROLLED STUDY; CYSTIC FIBROSIS; HUMAN; HUMAN CELL; INFECTION SENSITIVITY; LUNG INFECTION; MOUSE; NEWBORN; NONHUMAN; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; RESPIRATORY EPITHELIUM;

EID: 0030021470     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.271.5245.64     Document Type: Article

References (37)

1. M Aronson, O Medalia, D Amichay, O. Nativ. Infect Immun 56, 1615 (1988), E Dalal, O. Medalia, O Haran, M Aronson, ibid 62. 5505 (1994). S. Orikasa and F Hinman Jr., Invest. Urol 15, 185 (1977).
2. M Aronson, O Medalia, D Amichay, O. Nativ. Infect Immun 56, 1615 (1988), E Dalal, O. Medalia, O Haran, M Aronson, ibid 62. 5505 (1994). S. Orikasa and F Hinman Jr., Invest. Urol 15, 185 (1977).
3. M Aronson, O Medalia, D Amichay, O. Nativ. Infect Immun 56, 1615 (1988), E Dalal, O. Medalia, O Haran, M Aronson, ibid 62. 5505 (1994). S. Orikasa and F Hinman Jr., Invest. Urol 15, 185 (1977).
4. 5 epithelial cells Bacteria were allowed to be ingested by the epithelial cells for 3 or 4 hours at either 26° or 37°C, after which nonadherent bacteria were removed by washing. The remainder of the assay and controls were as described [S. M. J. Fleiszig, T. S Zaidi, G. B Pier. Infect immun. 63, 4072 (1995)]. Three to nine replicates were obtained per point and were analyzed by analysis of variance (ANOVA) and the Fisher PLSD statistic to determine pair-wise differences.
5. J C Olsen et al , Hum. Gene Ther. 3, 253 (1992); B. Sarkadi et al., J Biol Chem. 267, 2087 (1992).
6. J C Olsen et al , Hum. Gene Ther. 3, 253 (1992); B. Sarkadi et al., J Biol Chem. 267, 2087 (1992).
7. G. B. Pier, D. DesJardins, T. Aguilar, M. Barnard, D P. Speert, J Clin. Microbiol 24, 189 (1986)
8. G. M. Denning et al., Nature 358, 761 (1992), G M Denning, L S. Ostedgaard, M. J. Welsh, J Cell Biol. 118, 551 (1992); G M Denning, L. S. Ostedgaard, S H. Cheng, A E. Smith, M. J. Welsh, J Clin Invest 89, 339 (1992)
9. G. M. Denning et al., Nature 358, 761 (1992), G M Denning, L S. Ostedgaard, M. J. Welsh, J Cell Biol. 118, 551 (1992); G M Denning, L. S. Ostedgaard, S H. Cheng, A E. Smith, M. J. Welsh, J Clin Invest 89, 339 (1992)
10. G. M. Denning et al., Nature 358, 761 (1992), G M Denning, L S. Ostedgaard, M. J. Welsh, J Cell Biol. 118, 551 (1992); G M Denning, L. S. Ostedgaard, S H. Cheng, A E. Smith, M. J. Welsh, J Clin Invest 89, 339 (1992)
11. M. Grout and G. B. Pier, unpublished data
12. Human clinical isolates of bacterial pathogens that failed to be ingested by epithelial cells expressing wild-type CFTR differently from cells expressing ΔF508 mutant CFTR included the following Escherichia coli (two strains), Burkholderia cepacia (three strains), Neisseria meningitidis (one strain), Staphylococcus aureus (two strains), Staphylococcus epidermidis (two strains). Streptococcus pneumonias type XIV (one strain), and Streptococcus agalactiae (one strain)
13. D. E Ohman, J B Goldberg, J L. Flynn, in Pseudomonas: Biotransformations, Pathogenesis, and Evolving Biotechnology, S. Silver, A. Chakrabarty, B Iglewski, S. Kaplan, Eds (American Society for Microbiology, Washington, DC, 1990), pp 28-35; A Penketh, T. Pitt, D Roberts, M. E. Hodson, J. C Batten, Am. Hev. Respir Dis 127, 605 (1983) ; R E. W Hancock et al., Infect Immun. 42, 170 (1983); E Mahenthiralingam, M E Campbell, D P. Speert, ibid 62, 596 (199 4).
14. D. E Ohman, J B Goldberg, J L. Flynn, in Pseudomonas: Biotransformations, Pathogenesis, and Evolving Biotechnology, S. Silver, A. Chakrabarty, B Iglewski, S. Kaplan, Eds (American Society for Microbiology, Washington, DC, 1990), pp 28-35; A Penketh, T. Pitt, D Roberts, M. E. Hodson, J. C Batten, Am. Hev. Respir Dis 127, 605 (1983) ; R E. W Hancock et al., Infect Immun. 42, 170 (1983); E Mahenthiralingam, M E Campbell, D P. Speert, ibid 62, 596 (199 4).
15. D. E Ohman, J B Goldberg, J L. Flynn, in Pseudomonas: Biotransformations, Pathogenesis, and Evolving Biotechnology, S. Silver, A. Chakrabarty, B Iglewski, S. Kaplan, Eds (American Society for Microbiology, Washington, DC, 1990), pp 28-35; A Penketh, T. Pitt, D Roberts, M. E. Hodson, J. C Batten, Am. Hev. Respir Dis 127, 605 (1983) ; R E. W Hancock et al., Infect Immun. 42, 170 (1983); E Mahenthiralingam, M E Campbell, D P. Speert, ibid 62, 596 (199 4).
16. D. E Ohman, J B Goldberg, J L. Flynn, in Pseudomonas: Biotransformations, Pathogenesis, and Evolving Biotechnology, S. Silver, A. Chakrabarty, B Iglewski, S. Kaplan, Eds (American Society for Microbiology, Washington, DC, 1990), pp 28-35; A Penketh, T. Pitt, D Roberts, M. E. Hodson, J. C Batten, Am. Hev. Respir Dis 127, 605 (1983) ; R E. W Hancock et al., Infect Immun. 42, 170 (1983); E Mahenthiralingam, M E Campbell, D P. Speert, ibid 62, 596 (199 4).
17. A M Kropinski, L. C. Chan, F H. Milazzo, Can J. Microbiol 25, 390 (1979); S F. Koval and P. M Meadow, J. Gen. Microbiol 98, 387 (1977); P. S. Rowe and P. M. Meadow, Eur J. Biochem. 132, 329 (1983), K Jarrell and A M. Kropinski, Microbios 19, 103 (1977); M. J Coyne, K. S. Russell, C. L. Coyle, J. B Goldberg, J Bacteriol 176, 3500 (1994).
18. A M Kropinski, L. C. Chan, F H. Milazzo, Can J. Microbiol 25, 390 (1979); S F. Koval and P. M Meadow, J. Gen. Microbiol 98, 387 (1977); P. S. Rowe and P. M. Meadow, Eur J. Biochem. 132, 329 (1983), K Jarrell and A M. Kropinski, Microbios 19, 103 (1977); M. J Coyne, K. S. Russell, C. L. Coyle, J. B Goldberg, J Bacteriol 176, 3500 (1994).
19. A M Kropinski, L. C. Chan, F H. Milazzo, Can J. Microbiol 25, 390 (1979); S F. Koval and P. M Meadow, J. Gen. Microbiol 98, 387 (1977); P. S. Rowe and P. M. Meadow, Eur J. Biochem. 132, 329 (1983), K Jarrell and A M. Kropinski, Microbios 19, 103 (1977); M. J Coyne, K. S. Russell, C. L. Coyle, J. B Goldberg, J Bacteriol 176, 3500 (1994).
20. A M Kropinski, L. C. Chan, F H. Milazzo, Can J. Microbiol 25, 390 (1979); S F. Koval and P. M Meadow, J. Gen. Microbiol 98, 387 (1977); P. S. Rowe and P. M. Meadow, Eur J. Biochem. 132, 329 (1983), K Jarrell and A M. Kropinski, Microbios 19, 103 (1977); M. J Coyne, K. S. Russell, C. L. Coyle, J. B Goldberg, J Bacteriol 176, 3500 (1994).
21. A M Kropinski, L. C. Chan, F H. Milazzo, Can J. Microbiol 25, 390 (1979); S F. Koval and P. M Meadow, J. Gen. Microbiol 98, 387 (1977); P. S. Rowe and P. M. Meadow, Eur J. Biochem. 132, 329 (1983), K Jarrell and A M. Kropinski, Microbios 19, 103 (1977); M. J Coyne, K. S. Russell, C. L. Coyle, J. B Goldberg, J Bacteriol 176, 3500 (1994).
22. D. J Evans, G. B Pier, M J Coyne, J B Goldberg, Mol Microbiol 13, 427 (1994); J. B. Goldberg, K. Hatano, G S. Meluleni, G B. Pier. Proc. Natl. Acad. Sci U.S A 89, 10716 (1992).
23. D. J Evans, G. B Pier, M J Coyne, J B Goldberg, Mol Microbiol 13, 427 (1994); J. B. Goldberg, K. Hatano, G S. Meluleni, G B. Pier. Proc. Natl. Acad. Sci U.S A 89, 10716 (1992).
24. LPS was released from these strains by lysing bacterial cells grown on 25 petri plates containing tryptic soy agar with 1% sarcosyl in deionized water Cellular debris was removed by centrifugation at 20,000g for 15 min. and the LPS in the supernate purified as described [G. B Pier, H. F Sidberry, S Zolyomi, J. C Sadoff, Infect. Immun. 22, 908 (1978)] Purity and migration characteristics were confirmed in silverstained SDS-polyacrylamide gels. Lipid A was removed from LPS by suspending LPS in 1% acetic acid and heating the suspension for 3 hours at 95°C. Inhibition of ingestion in the presence of LPS was evaluated by adding LPS directly into wells during the bacterial ingestion assay. The highest doses of LPS were added to uninfected wells of epithelial cells to monitor for toxicity due to LPS Staining with trypan blue revealed no overt toxicity of the LPS preparations.
25. Although epithelial cells expressing mutant ΔF508 CFTR ingested the P aeruginosa expressing a complete LPS core better than they ingested bacteria expressing an incomplete LPS core (Fig 2) there was no statistically significant reduction in bacterial ingestion by mutant CFTR epithelial cells with complete-core LPS as an inhibitor This could be attributed either to an inability to measure further reductions in ingestion under circumstances in which the initial uptake is already quite low or to alternative ligand-receptor interactions between LPS-rough P aeruginosa and ΔF508 CFTR-expressing cells Purified O polysaccharides from LPS smooth wild-type strains did not inhibit bacterial ingestion by the airway epithelial cell lines
26. E T Schwan B D Robertson H Brade, J. P M Vanputten. Mol Microbiol 15. 267(1995)
27. H. Tang, M Kays A Prince Infect Immun 63, 1278 (1995)
28. R S Baltimore. C D C Christie GJW Smith, Am Rev Respir Dis 140, 1650 (1989). J W Nelson et al , Infect Immun 58, 1489 (1990), J. Lam, R Chan, K Lam J W Costerton, ibid 28, 546 (1980). P K Jeffery and P R Brain, Scanning Microsc 2. 553 (1988)
29. R S Baltimore. C D C Christie GJW Smith, Am Rev Respir Dis 140, 1650 (1989). J W Nelson et al , Infect Immun 58, 1489 (1990), J. Lam, R Chan, K Lam J W Costerton, ibid 28, 546 (1980). P K Jeffery and P R Brain, Scanning Microsc 2. 553 (1988)
30. R S Baltimore. C D C Christie GJW Smith, Am Rev Respir Dis 140, 1650 (1989). J W Nelson et al , Infect Immun 58, 1489 (1990), J. Lam, R Chan, K Lam J W Costerton, ibid 28, 546 (1980). P K Jeffery and P R Brain, Scanning Microsc 2. 553 (1988)
31. R S Baltimore. C D C Christie GJW Smith, Am Rev Respir Dis 140, 1650 (1989). J W Nelson et al , Infect Immun 58, 1489 (1990), J. Lam, R Chan, K Lam J W Costerton, ibid 28, 546 (1980). P K Jeffery and P R Brain, Scanning Microsc 2. 553 (1988)
32. L Saiman and A Prince, J Clin Invest 92, 1875 (1993). H Zar, L Saiman, L Ouittell. A Prince. J Pediatr 126, 230 (1995), L Imundo, J Barasch, A Prince, Q Al-Awqati, Proc. Natl Acad Sci U.S.A 92, 3019 (1995)
33. L Saiman and A Prince, J Clin Invest 92, 1875 (1993). H Zar, L Saiman, L Ouittell. A Prince. J Pediatr 126, 230 (1995), L Imundo, J Barasch, A Prince, Q Al-Awqati, Proc. Natl Acad Sci U.S.A 92, 3019 (1995)
34. L Saiman and A Prince, J Clin Invest 92, 1875 (1993). H Zar, L Saiman, L Ouittell. A Prince. J Pediatr 126, 230 (1995), L Imundo, J Barasch, A Prince, Q Al-Awqati, Proc. Natl Acad Sci U.S.A 92, 3019 (1995)
35. M. C Plotkowski, M. Chevillard, D Pierrot, D Altemayer, E Puchelle, J Med Microbiol 36, 104 (1992), M. A Cervin, D A Simpson, A L Smith, S Lory, Microb Pathog. 17, 291 (1994)
36. M. C Plotkowski, M. Chevillard, D Pierrot, D Altemayer, E Puchelle, J Med Microbiol 36, 104 (1992), M. A Cervin, D A Simpson, A L Smith, S Lory, Microb Pathog. 17, 291 (1994)
37. We thank D J Evans for constructing LPS-smocth recombinant P aeruginosa strains and SMJ Fleiszig for advice Supported by NIH grants to G B P (AI22806), to J C O. (HL42384), and to J B G (AI35674)