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J. Biol. Chem., Vol. 279, Issue 51, 52820-52823, December 17, 2004

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₂-Macroglobulin-Proteinase Complexes Protect Streptococcus pyogenes from Killing by the Antimicrobial Peptide LL-37^*

Patrik Nyberg, Magnus Rasmussen, and Lars Björck

From the Department of Cell and Molecular Biology, Section for Clinical and Experimental Infectious Medicine, Lund University, S-22184 Lund, Sweden

The significant human bacterial pathogen Streptococcus pyogenes expresses GRAB, a surface protein that binds ₂-macroglobulin (₂M), a major proteinase inhibitor of human plasma. ₂M inhibits proteolysis by trapping the proteinase, which, however, still remains proteolytically active against smaller peptides that can penetrate the ₂M-proteinase complex. Here we report that SpeB, a cysteine proteinase secreted by S. pyogenes, is trapped by ₂M 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.

Received for publication, October 13, 2004 , and in revised form, October 29, 2004.

^* This work was supported by grants from the Swedish Research Council (Projects 7480 and 14379), the Medical Faculty, Lund University, the Foundations of Kock and Österlund, and Hansa Medical AB. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Section for Clinical and Experimental Infectious Medicine, Dept. of Cell and Molecular Biology, Lund University, BMC, B14, Tornavägen 10, S-22184 Lund, Sweden. Tel.: 46-46-2224489; Fax: 46-46-157756; E-mail: Patrik.Nyberg{at}medkem.lu.se.

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