Group B streptococci escape host immunity by deletion of tandem repeat elements of the alpha C protein.
Group B streptococci (GBS) are the most common cause of neonatal sepsis, pneumonia, and meningitis. The alpha C protein is a surface-associated antigen; the gene (bca) for this protein contains a series of tandem repeats (each encoding 82 aa) that are identical at the nucleotide level and express a protective epitope. We previously reported that GBS isolates from two of 14 human maternal and neonatal pairs differed in the number of repeats contained in their alpha C protein; in both pairs, the alpha C protein of the neonatal isolate was smaller in molecular size. We now demonstrate by PCR that the neonatal isolates contain fewer tandem repeats. Maternal isolates were susceptible to opsonophagocytic killing in the presence of alpha C protein-specific antiserum, whereas the discrepant neonatal isolates proliferated. An animal model was developed to further study this phenomenon. Adult mice passively immunized with antiserum to the alpha C protein were challenged with an alpha C protein-expressing strain of GBS. Splenic isolates of GBS from these mice showed a high frequency of mutation in bca--most commonly a decrease in repeat number. Isolates from non-immune mice were not altered. Spontaneous deletions in the repeat region were observed at a much lower frequency (6 x 10(-4)); thus, deletions in that region are selected for under specific antibody pressure and appear to lower the organism's susceptibility to killing by antibody specific to the alpha C protein. This mechanism of antigenic variation may provide a means whereby GBS evade host immunity.
Madoff
L C
LC
Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA.
Michel
J L
JL
Gong
E W
EW
Kling
D E
DE
Kasper
D L
DL
D000818:Animals; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007106:Immune Sera; D007116:Immunization, Passive; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D051379:Mice; D008969:Molecular Sequence Data; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D013154:Spleen / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology* / Q000635:transmission; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification
D000954:Antigens, Surface; D001426:Bacterial Proteins; D017931:DNA Primers; D007106:Immune Sera; C077961:alpha C protein, group B streptococci