Genetic polymorphisms of group B streptococcus scpB alter functional activity of a cell-associated peptidase that inactivates C5a.
Many group B Streptococcus agalactiae strains and other pathogenic streptococci express a cell-associated peptidase that inactivates C5a (C5a-ase), the major neutrophil chemoattractant produced by activation of the complement cascade. Type III group B streptococci (GBS) can be classified genotypically into three restriction digest pattern types. Functional C5a-ase activity of GBS correlates with this genetic typing; therefore, we sought to identify a genetic basis for this phenomenon. Southern hybridization confirms that all type III GBS contain scpB, the gene encoding GBS C5a-ase. GBS strains with high C5a-ase functional activity and those with no or very low activity both express immunoreactive C5a-ase. The scpB sequence of strain I30, which has high C5a-ase activity, is 98.2% homologous to the previously reported serotype II GBS scpB sequence. The scpB sequences of strains I25 and GW, which have low or no C5a-ase activity, are identical. The predicted I25 and GW C5a-ase proteins share a four-amino-acid deletion affecting the protease histidine active-site consensus motif. Recombinant I30 C5a-ase has good functional activity, whereas recombinant I25 C5a-ase has low activity. These data demonstrate that functional C5a-ase differences between type III GBS strains are attributable to a genetic polymorphism of scpB. The ubiquitous expression of C5a-ase, irrespective of functional activity, suggests that C5a-ase may have a second, as yet unidentified, function.
Bohnsack
J F
JF
Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
Takahashi
S
S
Hammitt
L
L
Miller
D V
DV
Aly
A A
AA
Adderson
E E
EE
D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D005798:Genes, Bacterial; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000276:immunology
D018829:Adhesins, Bacterial; D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D010450:Endopeptidases; C053088:C5a peptidase