SpeB modulates fibronectin-dependent internalization of Streptococcus pyogenes by efficient proteolysis of cell-wall-anchored protein F1.
SpeB is a cysteine proteinase and virulence determinant secreted by the important human pathogen Streptococcus pyogenes. Recent investigations have suggested a role for SpeB in streptococcal entry into human cells. However, conflicting data concerning the contribution of SpeB to internalization have been presented. Protein F1 is a cell-wall-attached fibronectin (Fn)-binding protein that is present in a majority of streptococcal isolates and is important for internalization. This study shows that protein F1 is efficiently degraded by SpeB, and that removal of protein F1 from the bacterial surface leads to reduced internalization. Whereas M1 protein and protein H, two additional surface proteins of S. pyogenes that bind human plasma proteins, are protected from proteolytic degradation by their ligands, protein F1 is readily cleaved by SpeB also when in complex with Fn. This finding, and the connection between the presence of Fn at the bacterial surface and entry into human cells, suggest that SpeB plays a role in the regulation of the internalization process.
Nyberg
Patrik
P
Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, BMC, B14, Tornavägen 10, S-22184 Lund, Sweden.
Rasmussen
Magnus
M
Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, BMC, B14, Tornavägen 10, S-22184 Lund, Sweden.
von Pawel-Rammingen
Ulrich
U
Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, BMC, B14, Tornavägen 10, S-22184 Lund, Sweden.
Björck
Lars
L
Department of Cell and Molecular Biology, Section for Molecular Pathogenesis, Lund University, BMC, B14, Tornavägen 10, S-22184 Lund, Sweden.
D018829:Adhesins, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins; D002460:Cell Line; D002473:Cell Wall / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D005353:Fibronectins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D010614:Pharynx / Q000166:cytology / Q000382:microbiology; D013297:Streptococcus pyogenes / Q000201:enzymology / Q000254:growth & development / Q000472:pathogenicity*
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; C078635:fibronectin-binding proteins, bacterial; D003546:Cysteine Endopeptidases; C042477:streptopain