Insight of host immune evasion mediated by two variants of group A Streptococcus Mac protein

Johnson Agniswamy, Benfang Lei, James M. Musser, Peter D. Sun

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Group A Streptococcus has evolved numerous mechanisms to evade the host immune system to survive, disseminate, and cause disease. Recently a secreted protein named Mac-1 was identified and shown to enhance survival of the pathogen. A new variant of Mac-1 (designated Mac-2) also was recently described and shown to differ from Mac-1 by ∼50% amino acid sequence divergence in the middle one-third of the molecule. To gain new information about the role of Mac-1 and Mac-2 in host-pathogen interactions, solution binding experiments were performed using surface plasmon resonance and purified Mac proteins. Mac-1 bound the same lower hinge region of human IgG as Fc receptors with 2.5 μM affinity, which lead to proteolytic cleavage of the antibody. Similar K m (6.8-18.9 μM) and kcat (0.02-0.13 s-1) values of the Mac-1 endopeptidase activity were obtained for IgG1, IgG2, IgG3, and IgG4. Mac-2 variant, in contrast, bound human IgG poorly (KD = 16 mM) and had weak endopeptidase activity against IgG. Instead, Mac-2 bound FcγRII and FcγRIII with 5 and 75 μM affinity, respectively. This binding competitively blocked IgG from recognition by Fc receptors. Taken together, Mac proteins block immunoglobulin recognition by Fc receptors and degrade immunoglobulins, thereby enhancing survival of the pathogen through the inhibition of phagocytosis, endocytosis of IgG-opsonized particles, and antibody-dependent cell-mediated cytotoxicity. Consequently, these proteins may be potential therapeutic targets.

Original languageEnglish (US)
Pages (from-to)52789-52796
Number of pages8
JournalJournal of Biological Chemistry
Volume279
Issue number50
DOIs
StatePublished - Dec 10 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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