alpha2-Macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobial peptide LL-37.
The significant human bacterial pathogen Streptococcus pyogenes expresses GRAB, a surface protein that binds alpha(2)-macroglobulin (alpha(2)M), a major proteinase inhibitor of human plasma. alpha(2)M inhibits proteolysis by trapping the proteinase, which, however, still remains proteolytically active against smaller peptides that can penetrate the alpha(2)M-proteinase complex. Here we report that SpeB, a cysteine proteinase secreted by S. pyogenes, is trapped by alpha(2)M bound to protein GRAB. As a consequence, SpeB is retained at the bacterial surface and protects S. pyogenes against killing by the antibacterial peptide LL-37.
Nyberg
Patrik
P
Section for Clinical and Experimental Infectious Medicine, Department of Cell and Molecular Biology, Lund University, BMC, B14, Tornavägen 10, S-22184 Lund, Sweden. Patrik.Nyberg@medkem.lu.se
Rasmussen
Magnus
M
Björck
Lars
L
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000502:physiology*; D002352:Carrier Proteins / Q000737:chemistry* / Q000502:physiology*; D054804:Cathelicidins; D002498:Centrifugation; D003546:Cysteine Endopeptidases / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005098:Exotoxins / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D008954:Models, Biological; D010447:Peptide Hydrolases / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D013297:Streptococcus pyogenes / Q000737:chemistry*; D013997:Time Factors; D000511:alpha-Macroglobulins / Q000737:chemistry*
D023181:Antimicrobial Cationic Peptides; D001426:Bacterial Proteins; D002352:Carrier Proteins; D054804:Cathelicidins; D005098:Exotoxins; C119608:GRAB protein, Streptococcus pyogenes; D010455:Peptides; D000511:alpha-Macroglobulins; C027951:erythrogenic toxin; D010447:Peptide Hydrolases; D003546:Cysteine Endopeptidases