Rapid IgG heavy chain cleavage by the streptococcal IgG endopeptidase IdeS is mediated by IdeS monomers and is not due to enzyme dimerization

Vindebro, Reine; Spoerry, Christian; Pawel‐Rammingen, Ulrich von

doi:10.1016/j.febslet.2013.04.039

Cited by 29 publications

(29 citation statements)

References 25 publications

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“…Our results show that the AP M1T1 ( covS mutant) strains produce Mac/IdeS at sufficient concentrations to exert observable IgG cleavage activity. Our data further confirm that dimerization of Mac/IdeS is not required for cleavage activity (20). …”

Section: Resultssupporting

confidence: 83%

“…Proteolytic cleavage of IgG in the hinge region by Mac/IdeS is hypothesized to prevent the recognition of antibody-opsonized bacteria by Fc receptors of immune cells and by the complement system (17). Crystallization studies of Mac/IdeS suggested that protease activity depends on dimerization (18), but recent data show that it is highly unlikely that Mac/IdeS is active as a dimer (20) or that a putative dimer would be enzymatically more active than monomeric Mac/IdeS (20, 21). …”

Section: Introductionmentioning

confidence: 99%

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IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Okumura

Anderson

Döhrmann

et al. 2013

mBio

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The Mac/IdeS protein of group A Streptococcus (GAS) is a secreted cysteine protease with cleavage specificity for IgG and is highly expressed in the GAS serotype M1T1 clone, which is the serotype most frequently isolated from patients with life-threatening invasive infections. While studies of Mac/IdeS with recombinant protein have shown that the protein can potentially prevent opsonophagocytosis of GAS by neutrophils, the role of the protein in immune evasion as physiologically produced by the living organism has not been studied. Here we examined the contribution of Mac/IdeS to invasive GAS disease by generating a mutant lacking Mac/IdeS in the hyperinvasive M1T1 background. While Mac/IdeS was highly expressed and proteolytically active in the hyperinvasive strain, elimination of the bacterial protease did not significantly influence GAS phagocytic uptake, oxidative-burst induction, cathelicidin sensitivity, resistance to neutrophil or macrophage killing, or pathogenicity in pre- or postimmune mouse infectious challenges. We conclude that in the highly virulent M1T1 background, Mac/IdeS is not essential for either phagocyte resistance or virulence. Given the conservation of Mac/IdeS and homologues across GAS strains, it is possible that Mac/IdeS serves another important function in GAS ecology or contributes to virulence in other strain backgrounds.

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Section: Resultssupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Okumura

Anderson

Döhrmann

et al. 2013

mBio

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“…For in vitro testing, we used purified human monoclonal IgG antibodies (mAb) of subclass 1-4 and benchmarked the SRM-MS assays by side-by-side comparison with non-reducing SDS-PAGE ( Figure S2). The results reveal a sequential cleavage of all subclasses with a rapid generation of single cleaved IgG (scIgG) and a slower generation of fully digested IgG (F(ab')2 fragment) as previously reported (Vindebro et al, 2013). IgG3 is cleaved faster compared to the other subclasses and was fully digested after only 10 min of IdeS incubation ( Figure S2).…”

Section: Quantification Of the Proportions Between Ides Cleaved Igg Asupporting

confidence: 81%

Streptococcus pyogenesinfection and the human proteome with a special focus on the IgG-cleaving enzyme IdeS

Caq

Järnum

Winstedt

et al. 2017

Preprint

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Infectious diseases are characterized by a complex interplay between host and pathogen, but how these interactions impact the host proteome is unclear. Here we applied a novel mass spectrometry based proteomics strategy to investigate how the human proteome is transiently modified by the pathogen Streptococcus pyogenes, with a particular focus on bacterial cleavage of IgG in vivo. In invasive diseases, S. pyogenes evokes a massive host response in blood, whereas superficial diseases are characterized by a local leakage of several blood plasma proteins at the site of infection including IgG.S. pyogenes produces IdeS, a protease cleaving IgG in the lower hinge region and we find highly effective IdeS-cleavage of IgG in samples from local IgG poor microenvironments.The results show that IdeS contributes to the adaptation of S. pyogenes to its normal ecological niches. Additionally, the work identifies novel clinical opportunities for in vivo pathogen detection.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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“…To investigate whether IgG was involved in the OmpU-mediated bactericidal effect, the serum-killing assay was performed using NHS with or without treatment with IdeS, an IgG-specific cleavage protease of S. pyogenes [17,18]. When serum was pretreated with IdeS, survival of the wild-type A1552 and the Δ ompT mutant were about 60%, i.e.…”

Section: Resultsmentioning

confidence: 99%

Naturally Occurring IgG Antibodies Provide Innate Protection against <b><i>Vibrio cholerae </i></b>Bacteremia by Recognition of the Outer Membrane Protein U

et al. 2016

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Cholera epidemics are caused by Vibrio cholerae serogroups O1 and O139, whereas strains collectively known as non-O1/non-O139 V. cholerae are found in cases of extraintestinal infections and bacteremia. The mechanisms and factors influencing the occurrence of bacteremia and survival of V. cholerae in normal human serum have remained unclear. We found that naturally occurring IgG recognizing V. cholerae outer membrane protein U (OmpU) mediates a serum-killing effect in a complement C1q-dependent manner. Moreover, outer membrane vesicles (OMVs) containing OmpU caused enhanced survival of highly serum-sensitive classical V. cholerae in a dose-dependent manner. OMVs from wild-type and ompU mutant V. cholerae thereby provided a novel means to verify by extracellular transcomplementation the involvement of OmpU. Our data conclusively indicate that loss, or reduced expression, of OmpU imparts resistance to V. cholerae towards serum killing. We propose that the difference in OmpU protein levels is a plausible reason for differences in serum resistance and the ability to cause bacteremia observed among V. cholerae biotypes. Our findings provide a new perspective on how naturally occurring antibodies, perhaps induced by members of the microbiome, may play a role in the recognition of pathogens and the provocation of innate immune defense against bacteremia.

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Rapid IgG heavy chain cleavage by the streptococcal IgG endopeptidase IdeS is mediated by IdeS monomers and is not due to enzyme dimerization

Cited by 29 publications

References 25 publications

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

IgG Protease Mac/IdeS Is Not Essential for Phagocyte Resistance or Mouse Virulence of M1T1 Group A Streptococcus

Streptococcus pyogenesinfection and the human proteome with a special focus on the IgG-cleaving enzyme IdeS

Naturally Occurring IgG Antibodies Provide Innate Protection against <b><i>Vibrio cholerae </i></b>Bacteremia by Recognition of the Outer Membrane Protein U

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