Abstract
The effect of the M protein of Streptococcus equi subsp. equi on complement deposition, complement degradation, and bacterial survival in equine whole blood was examined in vitro. Preincubation of bacteria with rabbit M protein-specific immunoglobulin G (IgG) inhibited the survival of the M+ strain in whole blood by 20-fold (P < 0.01). In addition, preincubation of bacteria with M protein-specific F(ab')2 fragments inhibited the survival of M+ cells in whole blood by 3.8-fold (P < 0.01). In the absence of specific antibody, an M+ strain (CF32) of S. equi subsp. equi survived 100-fold better in whole blood than an M- isolate (strain 19) (P < 0.01). Complement inactivation by cobra venom factor significantly enhanced the ability of the M- and M+ strains of S. equi subsp. equi to survive in whole blood, the latter in the presence or absence of M protein-specific IgG. The major opsonic forms of C3, C3b and iC3b, were present on both M- and M+ cells after opsonization in nonimmune plasma. However, colloidal gold staining indicated that the M- strain bound four times as much C3 as the M+ strain (P < 0.02) and that preincubation of the M+ strain with M protein-specific IgG or F(ab')2 fragments also enhanced the amount of C3 deposited by a factor of 4 (P < 0.02). Therefore, at least part of the M protein's ability to enhance bacterial survival in equine whole blood may be related to its ability to interfere with the deposition of equine complement on the bacterial surface.
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- Beachey E. H. Type-specific opsonic antibodies evoked with a synthetic peptide of streptococcal M protein conjugated to polylysine without adjuvant. Infect Immun. 1986 Jan;51(1):362–364. doi: 10.1128/iai.51.1.362-364.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bermudez L. E., Young L. S., Enkel H. Interaction of Mycobacterium avium complex with human macrophages: roles of membrane receptors and serum proteins. Infect Immun. 1991 May;59(5):1697–1702. doi: 10.1128/iai.59.5.1697-1702.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bisno A. L. Alternate complement pathway activation by group A streptococci: role of M-protein. Infect Immun. 1979 Dec;26(3):1172–1176. doi: 10.1128/iai.26.3.1172-1176.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boschwitz J. S., Groschup M. H., Timoney J. F. A comparison of different methods of extraction of the M-protein from Streptococcus equi. Cornell Vet. 1991 Jan;81(1):25–36. [PubMed] [Google Scholar]
- Boschwitz J. S., Timoney J. F. Purification and characterization of equine complement factor C3. Vet Immunol Immunopathol. 1993 Sep;38(1-2):139–153. doi: 10.1016/0165-2427(93)90119-o. [DOI] [PubMed] [Google Scholar]
- Brown E. J., Hosea S. W., Hammer C. H., Burch C. G., Frank M. M. A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia. J Clin Invest. 1982 Jan;69(1):85–98. doi: 10.1172/JCI110444. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown E. J. Interaction of gram-positive microorganisms with complement. Curr Top Microbiol Immunol. 1985;121:159–187. doi: 10.1007/978-3-642-45604-6_8. [DOI] [PubMed] [Google Scholar]
- Brown E. J., Joiner K. A., Cole R. M., Berger M. Localization of complement component 3 on Streptococcus pneumoniae: anti-capsular antibody causes complement deposition on the pneumococcal capsule. Infect Immun. 1983 Jan;39(1):403–409. doi: 10.1128/iai.39.1.403-409.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brown E. J., Joiner K. A., Frank M. M. Interaction of desialated guinea pig erythrocytes with the classical and alternative pathways of guinea pig complement in vivo and in vitro. J Clin Invest. 1983 Jun;71(6):1710–1719. doi: 10.1172/JCI110925. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Campbell J. R., Baker C. J., Edwards M. S. Deposition and degradation of C3 on type III group B streptococci. Infect Immun. 1991 Jun;59(6):1978–1983. doi: 10.1128/iai.59.6.1978-1983.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dale J. B., Beachey E. H. Unique and common protective epitopes among different serotypes of group A streptococcal M proteins defined with hybridoma antibodies. Infect Immun. 1984 Oct;46(1):267–269. doi: 10.1128/iai.46.1.267-269.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fischetti V. A. Requirements for the opsonic activity of human IgG directed to type 6 group A streptococci: net basic charge and intact Fc region. J Immunol. 1983 Feb;130(2):896–902. [PubMed] [Google Scholar]
- Fischetti V. A. Streptococcal M protein. Sci Am. 1991 Jun;264(6):58–65. doi: 10.1038/scientificamerican0691-58. [DOI] [PubMed] [Google Scholar]
- Galán J. E., Timoney J. F. Immunologic and genetic comparison of Streptococcus equi isolates from the United States and Europe. J Clin Microbiol. 1988 Jun;26(6):1142–1146. doi: 10.1128/jcm.26.6.1142-1146.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gordon D. L., Rice J., Finlay-Jones J. J., McDonald P. J., Hostetter M. K. Analysis of C3 deposition and degradation on bacterial surfaces after opsonization. J Infect Dis. 1988 Apr;157(4):697–704. doi: 10.1093/infdis/157.4.697. [DOI] [PubMed] [Google Scholar]
- Griffin F. M., Jr, Griffin J. A., Leider J. E., Silverstein S. C. Studies on the mechanism of phagocytosis. I. Requirements for circumferential attachment of particle-bound ligands to specific receptors on the macrophage plasma membrane. J Exp Med. 1975 Nov 1;142(5):1263–1282. doi: 10.1084/jem.142.5.1263. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamlen H. J., Timoney J. F., Bell R. J. Epidemiologic and immunologic characteristics of Streptococcus equi infection in foals. J Am Vet Med Assoc. 1994 Mar 1;204(5):768–775. [PubMed] [Google Scholar]
- Hong K., Kinoshita T., Takeda J., Kozono H., Pramoonjago P., Kim Y. U., Inoue K. Inhibition of the alternative C3 convertase and classical C5 convertase of complement by group A streptococcal M protein. Infect Immun. 1990 Aug;58(8):2535–2541. doi: 10.1128/iai.58.8.2535-2541.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Horstmann R. D., Sievertsen H. J., Knobloch J., Fischetti V. A. Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1657–1661. doi: 10.1073/pnas.85.5.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hosea S. W., Brown E. J., Frank M. M. The critical role of complement in experimental pneumococcal sepsis. J Infect Dis. 1980 Dec;142(6):903–909. doi: 10.1093/infdis/142.6.903. [DOI] [PubMed] [Google Scholar]
- Jacks-Weis J., Kim Y., Cleary P. P. Restricted deposition of C3 on M+ group A streptococci: correlation with resistance to phagocytosis. J Immunol. 1982 Apr;128(4):1897–1902. [PubMed] [Google Scholar]
- Jean-François M. J., Poskitt D. C., Turnbull S. J., Macdonald L. M., Yasmeen D. Protection against Streptococcus equi infection by monoclonal antibodies against an M-like protein. J Gen Microbiol. 1991 Sep;137(9):2125–2133. doi: 10.1099/00221287-137-9-2125. [DOI] [PubMed] [Google Scholar]
- Kraus W., Haanes-Fritz E., Cleary P. P., Seyer J. M., Dale J. B., Beachey E. H. Sequence and type-specific immunogenicity of the amino-terminal region of type 1 streptococcal M protein. J Immunol. 1987 Nov 1;139(9):3084–3090. [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Ma J. K., Hunjan M., Smith R., Kelly C., Lehner T. An investigation into the mechanism of protection by local passive immunization with monoclonal antibodies against Streptococcus mutans. Infect Immun. 1990 Oct;58(10):3407–3414. doi: 10.1128/iai.58.10.3407-3414.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Muhktar M. M., Timoney J. F. Chemotactic response of equine polymorphonuclear leucocytes to Streptococcus equi. Res Vet Sci. 1988 Sep;45(2):225–229. [PubMed] [Google Scholar]
- Peterson P. K., Schmeling D., Cleary P. P., Wilkinson B. J., Kim Y., Quie P. G. Inhibition of alternative complement pathway opsonization by group A streptococcal M protein. J Infect Dis. 1979 May;139(5):575–585. doi: 10.1093/infdis/139.5.575. [DOI] [PubMed] [Google Scholar]
- Pilz D., Vocke T., Heesemann J., Brade V. Mechanism of YadA-mediated serum resistance of Yersinia enterocolitica serotype O3. Infect Immun. 1992 Jan;60(1):189–195. doi: 10.1128/iai.60.1.189-195.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Poirier T. P., Kehoe M. A., Whitnack E., Dockter M. E., Beachey E. H. Fibrinogen binding and resistance to phagocytosis of Streptococcus sanguis expressing cloned M protein of Streptococcus pyogenes. Infect Immun. 1989 Jan;57(1):29–35. doi: 10.1128/iai.57.1.29-35.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rice P. A., Vayo H. E., Tam M. R., Blake M. S. Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune serum. J Exp Med. 1986 Nov 1;164(5):1735–1748. doi: 10.1084/jem.164.5.1735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- STOLLERMAN G. H., EKSTEDT R. Long chain formation by strains of group A streptococci in the presence of homologous antiserum: a type-specific reaction. J Exp Med. 1957 Sep 1;106(3):345–356. doi: 10.1084/jem.106.3.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schlesinger L. S., Bellinger-Kawahara C. G., Payne N. R., Horwitz M. A. Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol. 1990 Apr 1;144(7):2771–2780. [PubMed] [Google Scholar]
- Sedgwick A. D., Morris T., Russell B. A., Lees P. Single step purification procedure for the rapid separation of equine leucocytes. Vet Res Commun. 1986 Nov;10(6):445–452. doi: 10.1007/BF02214007. [DOI] [PubMed] [Google Scholar]
- Stenberg L., O'Toole P., Lindahl G. Many group A streptococcal strains express two different immunoglobulin-binding proteins, encoded by closely linked genes: characterization of the proteins expressed by four strains of different M-type. Mol Microbiol. 1992 May;6(9):1185–1194. doi: 10.1111/j.1365-2958.1992.tb01557.x. [DOI] [PubMed] [Google Scholar]
- Timoney J. F., Trachman J. Immunologically reactive proteins of Streptococcus equi. Infect Immun. 1985 Apr;48(1):29–34. doi: 10.1128/iai.48.1.29-34.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Whitnack E., Beachey E. H. Antiopsonic activity of fibrinogen bound to M protein on the surface of group A streptococci. J Clin Invest. 1982 Apr;69(4):1042–1045. doi: 10.1172/JCI110508. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whitnack E., Beachey E. H. Inhibition of complement-mediated opsonization and phagocytosis of Streptococcus pyogenes by D fragments of fibrinogen and fibrin bound to cell surface M protein. J Exp Med. 1985 Dec 1;162(6):1983–1997. doi: 10.1084/jem.162.6.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woolcock J. B. Immunity to Streptococcus equi. Aust Vet J. 1975 Dec;51(12):554–559. doi: 10.1111/j.1751-0813.1975.tb09379.x. [DOI] [PubMed] [Google Scholar]
- Woolcock J. B. Purification and antigenicity of an M-like protein of Streptococcus equi. Infect Immun. 1974 Jul;10(1):116–122. doi: 10.1128/iai.10.1.116-122.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yarnall M., Widders P. R. Comparison of IgG Fc receptors from clinical isolates of Streptococcus zooepidemicus. J Med Microbiol. 1989 Feb;28(2):137–141. doi: 10.1099/00222615-28-2-137. [DOI] [PubMed] [Google Scholar]


