Abstract
The C protein α- and β-antigens are immunodominant components of the surface of Streptococcus agalactiae, the most frequent cause of neonatal sepsis. Both proteins are thought to contribute significantly to virulence of S. agalactiae. They are mainly expressed by serotypes Ia, Ib, and II. The C protein β-antigen (Cβ-protein) binds to the Fc portion of human IgA and seems to be of importance in bacterial resistance to mucosal immune defense mechanisms. In this study, PCR analysis of S. agalactiae isolates obtained from 189 neonates and 112 pregnant women revealed the presence of the Cβ-protein gene in 19% and 22% of the isolates, respectively. Size polymorphisms of the PCR products within the gene region encoding the cell wall–spanning domain indicated a high degree of genetic variability. Thirteen different variants of the amplified region were differentiated among the 60 Cβ-protein–positive isolates by sequence analysis. In all variants, the polymorphisms were caused by insertions and deletions of repetitive DNA elements that did not alter the open reading frame. Comparison of the Cβ-protein gene polymorphisms showed a significantly higher rate of isolates carrying deletions >50 bp in serotype Ib than in serotype II isolates (p = 0.001); this was also true for neonatal isolates analyzed separately (p = 0.01). Neonatal isolates carried a higher rate of large deletions when compared with maternal isolates; this difference, however, did not reach statistical significance (p = 0.08). We hypothesize that polymorphisms in the cell wall–spanning domain of the Cβ-protein are of functional relevance with regard to maternofetal transmission of the pathogen.
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Abbreviations
- Cβ-protein:
-
C protein β-antigen
- GBS:
-
group B streptococci Streptococcus agalactiae
References
Schuchat A 1998 Epidemiology of group B streptococcal disease in the United States: shifting paradigms. Clin Microbiol Rev 11: 497–513
Schuchat A, Zywicki SS, Dinsmoor MJ, Mercer B, Romaguera J, O'Sullivan MJ, Patel D, Peters MT, Stoll B, Levine OS 2000 The Prevention of Early-onset Neonatal Sepsis (PENS) Study Group, Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study. Pediatrics 105: 21–26
Baker CJ 1980 Group B streptococcal infections. Adv Intern Med 25: 475–501
Baker CJ, Barrett FF 1973 Transmission of group B streptococci among parturient women and their neonates. J Pediatr 83: 919–925
Berner R, Schumacher RF, Bartelt S, Forster J, Brandis M 1998 Predisposing conditions and pathogens in bacteremia in hospitalized children. Eur J Clin Microbiol Infect Dis 17: 337–340
Berner R, Niemeyer CM, Leititis JU, Funke A, Schwab C, Rau U, Richter K, Tawfeek MSK, Clad A, Brandis M 1998 Plasma levels and gene-expression of G-CSF, TNF-α, IL-1β, IL-6, IL-8, and sICAM-1 in neonatal early-onset sepsis. Pediatr Res 44: 469–477
Gladstone IM, Ehrenkranz RA, Edberg SC, Baltimore RS 1990 A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience. Pediatr Infect Dis J 9: 819–825
Siegel JD McCracken GH Jr 1981 Sepsis neonatorum. N Engl J Med 304: 642–647
Nizet V, Rubens CE 2000 Pathogenic mechanisms and virulence factors of group B streptococci. In: Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Rood JI(eds) Gram-Positive Pathogens. American Society for Microbiology Press, Washington, DC, pp 125–136
Paoletti LC, Madoff LC, Kasper DL 2000 Surface structures in group B streptococcus important in human immunity. In: Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Rood JI, (eds) Gram-Positive Pathogens. American Society for Microbiology Press, Washington, DC, pp 137–153
Rubens CE, Wessels MR, Heggen LM, Kasper DL 1987 Transposon mutagenesis of type III group B streptococcus: correlation of capsule expression with virulence. Proc Natl Acad Sci USA 84: 7208–7212
Wessels MR, Rubens CE, Benedi VJ, Kasper DL 1989 Definition of a bacterial virulence factor: sialysation of the group B streptococcal capsule. Proc Natl Acad Sci USA 86: 8983–8987
Berner R, Bender A, Rensing C, Forster J, Brandis M 1999 Low prevalence of the immunoglobulin A binding β antigen of the C protein among Streptococcus agalactiae isolates causing neonatal sepsis. Eur J Clin Microbiol Infect Dis 15: 545–550
Bevanger L 1983 Ibc proteins as serotype markers of group B streptococci. Acta Pathol Microbiol Immunol Scand Sect B 91: 231–234
Brady LJ, Daphtary UD, Ayoub EM, Boyle MDP 1988 Two novel antigens associated with group B streptococci identified by a rapid two-stage RIA. J Infect Dis 158: 965–972
Brady LJ, Boyle MDP 1989 Identification of non-immunoglobulin A-Fc-binding forms and low-molecular-weight secreted forms of the group B streptococcal beta antigen. Infect Immun 57: 1573–1581
Chun CSY, Brady LJ, Boyle MDP, Dillon HC, Ayoub EM 1991 Group B streptococcal C protein-associated antigens: association with neonatal sepsis. J Infect Dis 163: 786–791
Johnson DR, Ferrieri P 1984 Group B streptococcal Ibc protein antigen: distribution of two determinants of wild-type strains of common serotypes. J Clin Microbiol 19: 506–510
Kvam AI, Efstratiou A, Bevanger L, Cookson BD, Marticorenca IF, George RC, Maeland JA 1995 Distribution of serovariants of group B streptococci in isolates from England and Norway. J Med Microbiol 42: 246–250
Heden LO, Frithz E, Lindahl G 1991 Molecular characterization of an IgA receptor from group B streptococci: sequence of the structure and isolation of N-terminal fragments with IgA-binding capacity. Eur J Immunol 21: 1481–1490
Jerlstrom PG, Chhatwal GS, Timmis KN 1991 The IgA binding beta antigen for the C protein complex of group B streptococci: sequence determination of its gene and detection of two binding regions. Mol Microbiol 5: 843–849
Michel JL, Madoff LC, Olson K, Kling DE, Kasper DL, Ausubel FM 1992 Large, identical, tandem repeating units in the C protein alpha antigen gene, bca, of group B streptococci. Proc Natl Acad Sci USA 89: 10060–10064
Brady LJ, Daphtary UD, Ayoub EM, Boyle MDP 1988 Two novel antigens associated with group B streptococci identified by a rapid two-stage RIA. J Infect Dis 158: 965–972
Lancefield RC, McCarty M, Everly WN 1975 Multiple mouse-protective antibodies directed against group B streptococci. J Exp Med 142: 165–179
Payne NR, Ferrieri P 1985 The relation of the Ibc protein antigen to the opsonization differences between strains of type II group B streptococci. J Infect Dis 151: 672–681
Payne NR, Kim Y, Ferrieri P 1987 Effects of differences in antibody and complement requirements on phagocytic uptake and intracellular killing of “c” protein-positive and -negative strains of type II group B streptococci. Infect Immun 55: 1243–1251
Jerlstrom PG, Talay SR, Valentin-Weigand P, Timmis KN, Chhatwal GS 1996 Identification of an immunoglobulin A binding motif located in the β-antigen of the c protein complex of group B streptococci. Infect Immun 64: 2787–2793
Russell-Jones GJ, Gotschlich EC, Blake MS 1984 A surface receptor specific for human IgA on group B streptococci possessing the Ibc protein antigen. J Exp Med 160: 1467–1475
Madoff LC, Michel JL, Kasper DL 1991 A monoclonal antibody identifies a protective C protein alpha-antigen epitope in group B streptococci. Infect Immun 59: 204–210
Madoff LC, Paoletti LC, Tai JY, Kasper DL 1994 Maternal immunization of mice with group B streptococcal type III polysaccharide-beta C protein conjugate elicits protective antibody to multiple serotypes. J Clin Invest 94: 286–292
Michel JL, Madoff LC, Kling DE, Kasper DL, Ausubel FM 1991 Cloned alpha and beta C protein antigens of group B streptococci elicit protective immunity. Infect Immun 59: 2023–2028
Madoff LC, Hori S, Michel JL, Baker CJ, Kasper DL 1991 Phenotypic diversity in the alpha C protein of group B streptococci. Infect Immun 59: 2638–2644
Mawn JA, Simpson AJ, Heard SR 1993 Detection of the C protein gene among group B streptococci using PCR. J Clin Path 46: 633–636
Maeland JA, Brakstad OG, Bevanger L, Kvam AI 1997 Streptococcus agalactiae β gene and gene product variations. J Med Microbiol 46: 999–1005
Maeland JA, Bevanger L, Iversen G, Lyng RV 1999 bca, beta gene and gene product divergency in reference and prototype strains of Streptococcus agalactiae. Clin Diagn Lab Immunol 6: 986–988
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The authors thank Silvia Duerre for her excellent technical assistance.
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Supported by grants of the Deutsche Forschungsgemeinschaft (Be 1756/2-2).
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Berner, R., Ruess, M., Bereswill, S. et al. Polymorphisms in the Cell Wall–Spanning Domain of the C Protein β-Antigen in Clinical Streptococcus agalactiae Isolates Are Caused by Genetic Instability of Repeating DNA Sequences. Pediatr Res 51, 106–111 (2002). https://doi.org/10.1203/00006450-200201000-00019
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DOI: https://doi.org/10.1203/00006450-200201000-00019