alpha2-Macroglobulin-proteinase complexes protect Streptococcus pyogenes from killing by the antimicrobial peptide LL-37.
Nyberg. Patrik P; Rasmussen. Magnus M; Björck. Lars L
Key Findings
- Streptococcus pyogenes binds alpha‑2‑macroglobulin via its GRAB protein.
- Alpha‑2‑macroglobulin traps the bacterial cysteine protease SpeB but still allows it to stay active against small peptides.
- The alpha‑2‑macroglobulin‑SpeB complex on the bacterial surface protects the bacteria from being killed by LL‑37.
Practical Outcomes
- For those considering LL‑37 as a supplement or therapeutic, this research suggests that certain bacteria have built‑in defenses that can reduce its effectiveness. It highlights the importance of targeting bacterial resistance mechanisms alongside peptide use. No direct protocol changes are suggested, but it warns that LL‑37 may not work well against infections with Streptococcus pyogenes that express GRAB.
Summary
The study shows that the bacteria Streptococcus pyogenes can protect itself from the human antimicrobial peptide LL‑37 by using a surface protein (GRAB) that grabs a plasma protein (alpha‑2‑macroglobulin) which in turn traps a bacterial enzyme (SpeB). This complex stays on the bacterial surface and blocks LL‑37 from killing the bacteria.
Abstract
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.
Study Information
pubmed
2004
2004-11-01T00:00:00.000Z
10.1074/jbc.c400485200