Streptococcal DRS (distantly related to SIC) and SIC inhibit antimicrobial peptides, components of mucosal innate immunity: a comparison of their activities.
"Streptococcal inhibitor of complement" (SIC) and "distantly related to SIC" (DRS) are related virulence factors secreted by M1 and M12 strains of GAS, respectively. The human mucosal innate immune system, important components of which are beta-defensins, secretory leukocyte proteinase inhibitor (SLPI) and lysozyme, provides the first line of defence against microorganisms. We report the interaction between DRS and these proteins; further investigations into the interaction of SIC with the beta-defensins; and compare the sensitivity of M12 and M1 GAS to SLPI. We show that SLPI, which kills M1 GAS and is inhibited by SIC, cannot kill M12 GAS. DRS cannot inhibit SLPI killing of M1 GAS, although ELISA shows binding of DRS to SLPI. We suggest that the target for SLPI on M1 GAS resembles SIC, and soluble SIC inhibits by acting as a decoy for SLPI. M12 GAS may not have this target and cannot interact with SLPI. DRS inhibits the antibacterial action of hBD-2 and hBD-3. Binding of both SIC and DRS to hBD-2, and DRS to hBD-3, shows small positive enthalpy, suggesting that binding is largely hydrophobic. The data for SIC and hBD-3 indicate that this is not a homogeneous bimolecular interaction. We conclude that DRS shares several of the properties of SIC, and therefore can be considered an important virulence factor of M12 GAS and an aid to colonization of the host mucosae.
Fernie-King
Barbara A
BA
Microbial Immunology Group, Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
Seilly
David J
DJ
Binks
Michael J
MJ
Sriprakash
Kadaba S
KS
Lachmann
Peter J
PJ
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009113:Muramidase / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013297:Streptococcus pyogenes / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D023083:beta-Defensins / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D001426:Bacterial Proteins; C097739:SIC protein, Streptococcus; D053481:Secretory Leukocyte Peptidase Inhibitor; D037521:Virulence Factors; D023083:beta-Defensins; D009113:Muramidase