Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1997 Nov;65(11):4452–4459. doi: 10.1128/iai.65.11.4452-4459.1997

Comparative analysis of immunoglobulin A1 protease activity among bacteria representing different genera, species, and strains.

J Reinholdt 1, M Kilian 1
PMCID: PMC175640  PMID: 9353019

Abstract

Immunoglobulin A1 (IgA1) proteases cleaving human IgA1 in the hinge region are produced constitutively by a number of pathogens, including Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, and Streptococcus pneumoniae, as well as by some members of the resident oropharyngeal flora. Whereas IgA1 proteases have been shown to interfere with the functions of IgA antibodies in vitro, the exact role of these enzymes in the relationship of bacteria to a human host capable of responding with enzyme-neutralizing antibodies is not clear. Conceivably, the role of IgA1 proteases may depend on the quantity of IgA1 protease generated as well as on the balance between secreted and cell-associated forms of the enzyme. Therefore, we have compared levels of IgA1 protease activity in cultures of 38 bacterial strains representing different genera and species as well as strains of different pathogenic potential. Wide variation in activity generation rate was found overall and within some species. High activity was not an exclusive property of bacteria with documented pathogenicity. Almost all activity of H. influenzae, N. meningitidis, and N. gonorrhoeae strains was present in the supernatant. In contrast, large proportions of the activity in Streptococcus, Prevotella, and Capnocytophaga species was cell associated at early stationary phase, suggesting that the enzyme may play the role of a surface antigen. Partial release of cell-associated activity occurred during stationary phase. Within some taxa, the degree of activity variation correlated with degree of antigenic diversity of the enzyme as determined previously. This finding may indicate that the variation observed is of biological significance.

Full Text

The Full Text of this article is available as a PDF (229.1 KB).

Selected References

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

  1. Ahl T., Reinholdt J. Detection of immunoglobulin A1 protease-induced Fab alpha fragments on dental plaque bacteria. Infect Immun. 1991 Feb;59(2):563–569. doi: 10.1128/iai.59.2.563-569.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bachovchin W. W., Plaut A. G., Flentke G. R., Lynch M., Kettner C. A. Inhibition of IgA1 proteinases from Neisseria gonorrhoeae and Hemophilus influenzae by peptide prolyl boronic acids. J Biol Chem. 1990 Mar 5;265(7):3738–3743. [PubMed] [Google Scholar]
  3. Beighton D., Whiley R. A. Sialidase activity of the "Streptococcus milleri group" and other viridans group streptococci. J Clin Microbiol. 1990 Jun;28(6):1431–1433. doi: 10.1128/jcm.28.6.1431-1433.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brooks G. F., Lammel C. J., Blake M. S., Kusecek B., Achtman M. Antibodies against IgA1 protease are stimulated both by clinical disease and asymptomatic carriage of serogroup A Neisseria meningitidis. J Infect Dis. 1992 Dec;166(6):1316–1321. doi: 10.1093/infdis/166.6.1316. [DOI] [PubMed] [Google Scholar]
  5. Byers H. L., Homer K. A., Beighton D. Utilization of sialic acid by viridans streptococci. J Dent Res. 1996 Aug;75(8):1564–1571. doi: 10.1177/00220345960750080701. [DOI] [PubMed] [Google Scholar]
  6. Devenyi A. G., Plaut A. G., Grundy F. J., Wright A. Post-infectious human serum antibodies inhibit IgA1 proteinases by interaction with the cleavage site specificity determinant. Mol Immunol. 1993 Oct;30(14):1243–1248. doi: 10.1016/0161-5890(93)90039-e. [DOI] [PubMed] [Google Scholar]
  7. Frandsen E. V., Reinholdt J., Kilian M. Enzymatic and antigenic characterization of immunoglobulin A1 proteases from Bacteroides and Capnocytophaga spp. Infect Immun. 1987 Mar;55(3):631–638. doi: 10.1128/iai.55.3.631-638.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gilbert J. V., Plaut A. G., Longmaid B., Lamm M. E. Inhibition of microbial IgA proteases by human secretory IgA and serum. Mol Immunol. 1983 Sep;20(9):1039–1049. doi: 10.1016/0161-5890(83)90045-7. [DOI] [PubMed] [Google Scholar]
  9. Gilbert J. V., Plaut A. G., Wright A. Analysis of the immunoglobulin A protease gene of Streptococcus sanguis. Infect Immun. 1991 Jan;59(1):7–17. doi: 10.1128/iai.59.1.7-17.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gray-Owen S. D., Schryvers A. B. Bacterial transferrin and lactoferrin receptors. Trends Microbiol. 1996 May;4(5):185–191. doi: 10.1016/0966-842x(96)10025-1. [DOI] [PubMed] [Google Scholar]
  11. Grundy F. J., Plaut A. G., Wright A. Localization of the cleavage site specificity determinant of Haemophilus influenzae immunoglobulin A1 protease genes. Infect Immun. 1990 Feb;58(2):320–331. doi: 10.1128/iai.58.2.320-331.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Halter R., Pohlner J., Meyer T. F. Mosaic-like organization of IgA protease genes in Neisseria gonorrhoeae generated by horizontal genetic exchange in vivo. EMBO J. 1989 Sep;8(9):2737–2744. doi: 10.1002/j.1460-2075.1989.tb08415.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hauck C. R., Meyer T. F. The lysosomal/phagosomal membrane protein h-lamp-1 is a target of the IgA1 protease of Neisseria gonorrhoeae. FEBS Lett. 1997 Mar 17;405(1):86–90. doi: 10.1016/s0014-5793(97)00163-4. [DOI] [PubMed] [Google Scholar]
  14. Jensen S. B., Löe H., Schiött C. R., Theliade E. Experimental gingivitis in man. 4. Vancomycin induced changes in bacterial plaque composition as related to development of gingival inflammation. J Periodontal Res. 1968;3(4):284–293. doi: 10.1111/j.1600-0765.1968.tb01934.x. [DOI] [PubMed] [Google Scholar]
  15. Kett K., Brandtzaeg P., Radl J., Haaijman J. J. Different subclass distribution of IgA-producing cells in human lymphoid organs and various secretory tissues. J Immunol. 1986 May 15;136(10):3631–3635. [PubMed] [Google Scholar]
  16. Kilian M. Degradation of immunoglobulins A2, A2, and G by suspected principal periodontal pathogens. Infect Immun. 1981 Dec;34(3):757–765. doi: 10.1128/iai.34.3.757-765.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kilian M., Husby S., Høst A., Halken S. Increased proportions of bacteria capable of cleaving IgA1 in the pharynx of infants with atopic disease. Pediatr Res. 1995 Aug;38(2):182–186. doi: 10.1203/00006450-199508000-00008. [DOI] [PubMed] [Google Scholar]
  18. Kilian M., Mestecky J., Kulhavy R., Tomana M., Butler W. T. IgA1 proteases from Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, and Streptococcus sanguis: comparative immunochemical studies. J Immunol. 1980 Jun;124(6):2596–2600. [PubMed] [Google Scholar]
  19. Kilian M., Mestecky J., Russell M. W. Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Microbiol Rev. 1988 Jun;52(2):296–303. doi: 10.1128/mr.52.2.296-303.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kilian M., Reinholdt J., Lomholt H., Poulsen K., Frandsen E. V. Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. APMIS. 1996 May;104(5):321–338. doi: 10.1111/j.1699-0463.1996.tb00724.x. [DOI] [PubMed] [Google Scholar]
  21. Kilian M., Thomsen B., Petersen T. E., Bleeg H. Molecular biology of Haemophilus influenzae IgA1 proteases. Mol Immunol. 1983 Sep;20(9):1051–1058. doi: 10.1016/0161-5890(83)90046-9. [DOI] [PubMed] [Google Scholar]
  22. Kornfeld S. J., Plaut A. G. Secretory immunity and the bacterial IgA proteases. Rev Infect Dis. 1981 May-Jun;3(3):521–534. doi: 10.1093/clinids/3.3.521. [DOI] [PubMed] [Google Scholar]
  23. Lomholt H. Evidence of recombination and an antigenically diverse immunoglobulin A1 protease among strains of Streptococcus pneumoniae. Infect Immun. 1995 Nov;63(11):4238–4243. doi: 10.1128/iai.63.11.4238-4243.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lomholt H., Kilian M. Antigenic relationships among immunoglobulin A1 proteases from Haemophilus, Neisseria, and Streptococcus species. Infect Immun. 1994 Aug;62(8):3178–3183. doi: 10.1128/iai.62.8.3178-3183.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lomholt H., Kilian M. Distinct antigenic and genetic properties of the immunoglobulin A1 protease produced by Haemophilus influenzae biogroup aegyptius associated with Brazilian purpuric fever in Brazil. Infect Immun. 1995 Nov;63(11):4389–4394. doi: 10.1128/iai.63.11.4389-4394.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lomholt H. Molecular biology and vaccine aspects of bacterial immunoglobulin A1 proteases. APMIS Suppl. 1996;62:5–28. doi: 10.1111/j.1600-0463.1996.tb05580.x. [DOI] [PubMed] [Google Scholar]
  27. Lomholt H., Poulsen K., Kilian M. Comparative characterization of the iga gene encoding IgA1 protease in Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae. Mol Microbiol. 1995 Feb;15(3):495–506. doi: 10.1111/j.1365-2958.1995.tb02263.x. [DOI] [PubMed] [Google Scholar]
  28. Lomholt H., van Alphen L., Kilian M. Antigenic variation of immunoglobulin A1 proteases among sequential isolates of Haemophilus influenzae from healthy children and patients with chronic obstructive pulmonary disease. Infect Immun. 1993 Nov;61(11):4575–4581. doi: 10.1128/iai.61.11.4575-4581.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mekalanos J. J. Environmental signals controlling expression of virulence determinants in bacteria. J Bacteriol. 1992 Jan;174(1):1–7. doi: 10.1128/jb.174.1.1-7.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Meyer T. F., Pohlner J., van Putten J. P. Biology of the pathogenic Neisseriae. Curr Top Microbiol Immunol. 1994;192:283–317. doi: 10.1007/978-3-642-78624-2_13. [DOI] [PubMed] [Google Scholar]
  31. Milazzo F. H., Delisle G. J. Immunoglobulin A proteases in gram-negative bacteria isolated from human urinary tract infections. Infect Immun. 1984 Jan;43(1):11–13. doi: 10.1128/iai.43.1.11-13.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mortensen S. B., Kilian M. Purification and characterization of an immunoglobulin A1 protease from Bacteroides melaninogenicus. Infect Immun. 1984 Sep;45(3):550–557. doi: 10.1128/iai.45.3.550-557.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Navarre W. W., Schneewind O. Proteolytic cleavage and cell wall anchoring at the LPXTG motif of surface proteins in gram-positive bacteria. Mol Microbiol. 1994 Oct;14(1):115–121. doi: 10.1111/j.1365-2958.1994.tb01271.x. [DOI] [PubMed] [Google Scholar]
  34. Nyvad B., Kilian M. Microbiology of the early colonization of human enamel and root surfaces in vivo. Scand J Dent Res. 1987 Oct;95(5):369–380. doi: 10.1111/j.1600-0722.1987.tb01627.x. [DOI] [PubMed] [Google Scholar]
  35. Plaut A. G., Qiu J., Grundy F., Wright A. Growth of Haemophilus influenzae in human milk: synthesis, distribution, and activity of IgA protease as determined by study of iga+ and mutant iga- cells. J Infect Dis. 1992 Jul;166(1):43–52. doi: 10.1093/infdis/166.1.43. [DOI] [PubMed] [Google Scholar]
  36. Plaut A. G. The IgA1 proteases of pathogenic bacteria. Annu Rev Microbiol. 1983;37:603–622. doi: 10.1146/annurev.mi.37.100183.003131. [DOI] [PubMed] [Google Scholar]
  37. Pohlner J., Halter R., Beyreuther K., Meyer T. F. Gene structure and extracellular secretion of Neisseria gonorrhoeae IgA protease. 1987 Jan 29-Feb 4Nature. 325(6103):458–462. doi: 10.1038/325458a0. [DOI] [PubMed] [Google Scholar]
  38. Poulsen K., Reinholdt J., Kilian M. A comparative genetic study of serologically distinct Haemophilus influenzae type 1 immunoglobulin A1 proteases. J Bacteriol. 1992 May;174(9):2913–2921. doi: 10.1128/jb.174.9.2913-2921.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Poulsen K., Reinholdt J., Kilian M. Characterization of the Streptococcus pneumoniae immunoglobulin A1 protease gene (iga) and its translation product. Infect Immun. 1996 Oct;64(10):3957–3966. doi: 10.1128/iai.64.10.3957-3966.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Reinholdt J. A method for titration of inhibiting antibodies to bacterial immunoglobulin A1 proteases in human serum and secretions. J Immunol Methods. 1996 May 10;191(1):39–48. doi: 10.1016/0022-1759(95)00286-3. [DOI] [PubMed] [Google Scholar]
  41. Reinholdt J., Kilian M. Titration of inhibiting antibodies to bacterial IgA1 proteases in human sera and secretions. Adv Exp Med Biol. 1995;371A:605–608. doi: 10.1007/978-1-4615-1941-6_127. [DOI] [PubMed] [Google Scholar]
  42. Reinholdt J., Tomana M., Mortensen S. B., Kilian M. Molecular aspects of immunoglobulin A1 degradation by oral streptococci. Infect Immun. 1990 May;58(5):1186–1194. doi: 10.1128/iai.58.5.1186-1194.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Shoberg R. J., Mulks M. H. Proteolysis of bacterial membrane proteins by Neisseria gonorrhoeae type 2 immunoglobulin A1 protease. Infect Immun. 1991 Aug;59(8):2535–2541. doi: 10.1128/iai.59.8.2535-2541.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Simpson D. A., Hausinger R. P., Mulks M. H. Purification, characterization, and comparison of the immunoglobulin A1 proteases of Neisseria gonorrhoeae. J Bacteriol. 1988 Apr;170(4):1866–1873. doi: 10.1128/jb.170.4.1866-1873.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sørensen C. H., Kilian M. Bacterium-induced cleavage of IgA in nasopharyngeal secretions from atopic children. Acta Pathol Microbiol Immunol Scand C. 1984 Feb;92(1):85–87. doi: 10.1111/j.1699-0463.1984.tb00056.x. [DOI] [PubMed] [Google Scholar]
  46. Thiesen B., Greenwood B., Brieske N., Achtman M. Persistence of antibodies to meningococcal IgA1 protease versus decay of antibodies to group A polysaccharide and Opc protein. Vaccine. 1997 Feb;15(2):209–219. doi: 10.1016/s0264-410x(96)00138-7. [DOI] [PubMed] [Google Scholar]
  47. Wani J. H., Gilbert J. V., Plaut A. G., Weiser J. N. Identification, cloning, and sequencing of the immunoglobulin A1 protease gene of Streptococcus pneumoniae. Infect Immun. 1996 Oct;64(10):3967–3974. doi: 10.1128/iai.64.10.3967-3974.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES