Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1989 Oct;57(10):3038–3044. doi: 10.1128/iai.57.10.3038-3044.1989

Antigenic drift of Haemophilus influenzae in patients with chronic obstructive pulmonary disease.

K Groeneveld 1, L van Alphen 1, C Voorter 1, P P Eijk 1, H M Jansen 1, H C Zanen 1
PMCID: PMC260767  PMID: 2789192

Abstract

Differences in the major outer membrane protein b,c (molecular weight, 39,000 to 41,000) of related Haemophilus influenzae strains isolated from the sputum of patients with chronic obstructive pulmonary disease were analyzed biochemically and immunologically. Protein b,c was isolated from a total of six related H. influenzae strains from two chronic obstructive pulmonary disease patients. After CNBr digestion of the proteins, the differences in size appeared in the larger of the two fragments. Trypsin and chymotrypsin digests of proteins from related H. influenzae strains showed that proteins differed by only a few peptides or were very similar, in contrast to the peptide maps of proteins from nonrelated strains. Peptide analysis of b,c proteins from related H. influenzae strains by high-performance liquid chromatography after Staphylococcus aureus V8 protease digestion and amino acid analysis of corresponding fractions revealed highly comparable patterns, indicating only minor differences in the amino acid sequences of these proteins. Immunization of rabbits with intact bacteria of four related H. influenzae strains resulted in a strong anti-protein b,c antibody response in all animals. In three of four rabbits, antibodies specific for the b,c protein of the strain used for immunization were elicited, indicating that the changed proteins contained specific immunodominant epitopes. Anti-protein b,c antibodies promoted strain-specific, complement-dependent, bactericidal activity. From these results, we conclude that H. influenzae shows antigenic drift in immunodominant epitopes, caused by small changes in amino acid composition of the b,c protein. Antibodies to these epitopes promote complement-dependent bactericidal activity.

Full text

PDF
3038

Images in this article

3039Image
on p.3039
3039Image
on p.3039
3041Image
on p.3041
3041Image
on p.3041
3041Image
on p.3041

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amons R., Schrier P. I. Removal of sodium dodecyl sulfate from proteins and peptides by gel filtration. Anal Biochem. 1981 Sep 15;116(2):439–443. doi: 10.1016/0003-2697(81)90385-7. [DOI] [PubMed] [Google Scholar]
  2. Barenkamp S. J., Shurin P. A., Marchant C. D., Karasic R. B., Pelton S. I., Howie V. M., Granoff D. M. Do children with recurrent Haemophilus influenzae otitis media become infected with a new organism or reacquire the original strain? J Pediatr. 1984 Oct;105(4):533–537. doi: 10.1016/s0022-3476(84)80415-1. [DOI] [PubMed] [Google Scholar]
  3. Dunn S. D. Effects of the modification of transfer buffer composition and the renaturation of proteins in gels on the recognition of proteins on Western blots by monoclonal antibodies. Anal Biochem. 1986 Aug 15;157(1):144–153. doi: 10.1016/0003-2697(86)90207-1. [DOI] [PubMed] [Google Scholar]
  4. Groeneveld K., van Alphen L., Eijk P. P., Jansen H. M., Zanen H. C. Changes in outer membrane proteins of nontypable Haemophilus influenzae in patients with chronic obstructive pulmonary disease. J Infect Dis. 1988 Aug;158(2):360–365. doi: 10.1093/infdis/158.2.360. [DOI] [PubMed] [Google Scholar]
  5. Hollingshead S. K., Fischetti V. A., Scott J. R. Size variation in group A streptococcal M protein is generated by homologous recombination between intragenic repeats. Mol Gen Genet. 1987 May;207(2-3):196–203. doi: 10.1007/BF00331578. [DOI] [PubMed] [Google Scholar]
  6. Jones K. F., Hollingshead S. K., Scott J. R., Fischetti V. A. Spontaneous M6 protein size mutants of group A streptococci display variation in antigenic and opsonogenic epitopes. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8271–8275. doi: 10.1073/pnas.85.21.8271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Karasic R. B., Trumpp C. E., Gnehm H. E., Rice P. A., Pelton S. I. Modification of otitis media in chinchillas rechallenged with nontypable Haemophilus influenzae and serological response to outer membrane antigens. J Infect Dis. 1985 Feb;151(2):273–279. doi: 10.1093/infdis/151.2.273. [DOI] [PubMed] [Google Scholar]
  8. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  9. Lugtenberg B., Meijers J., Peters R., van der Hoek P., van Alphen L. Electrophoretic resolution of the "major outer membrane protein" of Escherichia coli K12 into four bands. FEBS Lett. 1975 Oct 15;58(1):254–258. doi: 10.1016/0014-5793(75)80272-9. [DOI] [PubMed] [Google Scholar]
  10. Munson R. S., Jr, Granoff D. M. Purification and partial characterization of outer membrane proteins P5 and P6 from Haemophilus influenzae type b. Infect Immun. 1985 Sep;49(3):544–549. doi: 10.1128/iai.49.3.544-549.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Munson R. S., Jr, Shenep J. L., Barenkamp S. J., Granoff D. M. Purification and comparison of outer membrane protein P2 from Haemophilus influenzae type b isolates. J Clin Invest. 1983 Aug;72(2):677–684. doi: 10.1172/JCI111017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Munson R., Jr, Tolan R. W., Jr Molecular cloning, expression, and primary sequence of outer membrane protein P2 of Haemophilus influenzae type b. Infect Immun. 1989 Jan;57(1):88–94. doi: 10.1128/iai.57.1.88-94.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Murphy T. F., Apicella M. A. Antigenic heterogeneity of outer membrane proteins of nontypable Haemophilus influenzae is a basis for a serotyping system. Infect Immun. 1985 Oct;50(1):15–21. doi: 10.1128/iai.50.1.15-21.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Murphy T. F., Apicella M. A. Nontypable Haemophilus influenzae: a review of clinical aspects, surface antigens, and the human immune response to infection. Rev Infect Dis. 1987 Jan-Feb;9(1):1–15. doi: 10.1093/clinids/9.1.1. [DOI] [PubMed] [Google Scholar]
  15. Murphy T. F., Bartos L. C. Human bactericidal antibody response to outer membrane protein P2 of nontypeable Haemophilus influenzae. Infect Immun. 1988 Oct;56(10):2673–2679. doi: 10.1128/iai.56.10.2673-2679.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Murphy T. F., Bartos L. C. Purification and analysis with monoclonal antibodies of P2, the major outer membrane protein of nontypable Haemophilus influenzae. Infect Immun. 1988 May;56(5):1084–1089. doi: 10.1128/iai.56.5.1084-1089.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Murphy T. F., Bartos L. C., Rice P. A., Nelson M. B., Dudas K. C., Apicella M. A. Identification of a 16,600-dalton outer membrane protein on nontypeable Haemophilus influenzae as a target for human serum bactericidal antibody. J Clin Invest. 1986 Oct;78(4):1020–1027. doi: 10.1172/JCI112656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Murphy T. F., Bernstein J. M., Dryja D. M., Campagnari A. A., Apicella M. A. Outer membrane protein and lipooligosaccharide analysis of paired nasopharyngeal and middle ear isolates in otitis media due to nontypable Haemophilus influenzae: pathogenetic and epidemiological observations. J Infect Dis. 1987 Nov;156(5):723–731. doi: 10.1093/infdis/156.5.723. [DOI] [PubMed] [Google Scholar]
  19. Poolman J. T., Hopman C. T., Zanen H. C. Immunochemical characterization of Neisseria meningitidis serotype antigens by immunodiffusion and SDS-polyacrylamide gel electrophoresis immunoperoxidase techniques and the distribution of serotypes among cases and carriers. J Gen Microbiol. 1980 Feb;116(2):465–473. doi: 10.1099/00221287-116-2-465. [DOI] [PubMed] [Google Scholar]
  20. Swank R. T., Munkres K. D. Molecular weight analysis of oligopeptides by electrophoresis in polyacrylamide gel with sodium dodecyl sulfate. Anal Biochem. 1971 Feb;39(2):462–477. doi: 10.1016/0003-2697(71)90436-2. [DOI] [PubMed] [Google Scholar]
  21. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. van Alphen L., van den Berghe N., Geelen-van den Broek L. Interaction of Haemophilus influenzae with human erythrocytes and oropharyngeal epithelial cells is mediated by a common fimbrial epitope. Infect Immun. 1988 Jul;56(7):1800–1806. doi: 10.1128/iai.56.7.1800-1806.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES

HHS Vulnerability Disclosure