Group A streptococcal phagocytosis resistance is independent of complement factor H and factor H-like protein 1 binding.
Factor H (FH) and factor H-like protein 1 (FHL-1) regulate complement activation through the alternative pathway. Several extracellular bacterial pathogens, prime targets for the complement system, bind FH and FHL-1, thereby acquiring a potential mechanism for minimizing complement deposition on their surface. For group A streptococci (GAS), surface-bound antiphagocytic M proteins mediate the interaction. To study the role of the FH-FHL-1 interaction for complement deposition and opsonophagocytosis of GAS, we first constructed a set of truncated M5 protein variants and expressed them on the surface of a homologous M-negative GAS strain. Binding experiments with the resulting strains demonstrated that the major FH-FHL-1 binding is located in a 42-amino-acid region within the N-terminal third of M5. Measurement of bacteria-bound complement factor C3 after incubation in plasma showed that the presence of this region had little impact upon complement deposition through the alternative pathway. Moreover, streptococci expressing M5 proteins lacking the major FH and FHL-1 binding sequence resisted phagocytosis in human blood as efficiently as bacteria expressing the wild-type protein. Consequently, the data suggest that the binding of the regulators of the alternative pathway is of limited importance for GAS phagocytosis resistance.
Kotarsky
H
H
Section for Microbiology, Immunology and Glycobiology, Institute of Laboratory Medicine, Lund University, Biomedical Center, B14, S-221 84 Lund, Sweden. heike.kotarsky@mig.lu.se
Gustafsson
M
M
Svensson
H G
HG
Zipfel
P F
PF
Truedsson
L
L
Sjöbring
U
U
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001798:Blood Proteins / Q000276:immunology / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism; D017242:Complement Factor H / Q000276:immunology / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D010587:Phagocytosis; D011485:Protein Binding; D017384:Sequence Deletion; D013291:Streptococcus / Q000145:classification / Q000254:growth & development / Q000276:immunology / Q000378:metabolism*
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001798:Blood Proteins; C493495:CFH protein, human; D002352:Carrier Proteins; D003180:Complement C3b Inactivator Proteins; D017931:DNA Primers; C100631:factor H-related protein 1; C014689:streptococcal M protein; D003179:Complement C3b; D017242:Complement Factor H