2008
DOI: 10.1128/iai.01422-07
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The Intrinsic Immunoglobulin G Endopeptidase Activity of Streptococcal Mac-2 Proteins Implies a Unique Role for the Enzymatically Impaired Mac-2 Protein of M28 Serotype Strains

Abstract: IdeS, a secreted cysteine protease of the important human pathogen Streptococcus pyogenes, interferes with phagocytic killing by specifically cleaving the heavy chain of immunoglobulin G (IgG). Two allelic variants of the enzyme have been described, the IgG-specific endopeptidase, IdeS (or Mac-1) and Mac-2, a protein with only weak IgG endopeptidase activity, which has been suggested to interfere with opsonophagocytosis by blocking Fc␥ receptors of phagocytic cells. However, despite the fact that Mac-2 protein… Show more

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Cited by 26 publications
(27 citation statements)
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“…Notably, in the presence of SpeB protein, i.e., independently of enzymatic activity, the amount of extracellular ROS is clearly diminished compared to that of the control (Fig. 2B), an observation also reported for IdeS, another streptococcal cysteine protease (38).…”
Section: Discussionsupporting
confidence: 50%
“…Notably, in the presence of SpeB protein, i.e., independently of enzymatic activity, the amount of extracellular ROS is clearly diminished compared to that of the control (Fig. 2B), an observation also reported for IdeS, another streptococcal cysteine protease (38).…”
Section: Discussionsupporting
confidence: 50%
“…It bound soluble FcgRII and FcgRIII and competed with IgG binding (29), as well as prevented the generation of reactive oxygen species by opsonized latex beads. However, in a whole-blood survival assay of S. pyogenes, only Mac-2 with intact IgG endopeptidase activity facilitated bacterial survival (35). To our knowledge, no other bacterial FcgR antagonist has been described; therefore, this is the first study to demonstrate a bacterial FcgR-binding protein that inhibits FcgR-mediated effector functions in vitro, as well as in vivo.…”
Section: Discussionmentioning
confidence: 85%
“…The striking increase in HA capsule production observed in several GAS strains in response to LL-37 could, by itself, result in increased resistance to phagocytosis, enhanced invasion across host epithelial barriers, and increased overall virulence (29,30). Similar changes in expression of other CsrRS-regulated genes, such as the antiphagocytic Mac/IdeS and the IL-8 protease PrtS, are likely to further enhance pathogenicity (31)(32)(33). To test this prediction, we assessed the effect of LL-37 on GAS resistance to complement-mediated opsonophagocytic killing using 4 GAS isolates that exhibited moderate to strong up-regulation of capsule and other CsrRS-regulated genes in response to LL-37: strains 854, 94459, 02-123-1579, and SS-108.…”
Section: Ll-37 Up-regulates Capsular Polysaccharide Production In Mulmentioning
confidence: 99%