Cysteine proteinase SpeB from Streptococcus pyogenes – a potent modifier of immunologically important host and bacterial proteins

@inproceedings{Nelson2011CysteinePS,
  title={Cysteine proteinase SpeB from Streptococcus pyogenes – a potent modifier of immunologically important host and bacterial proteins},
  author={Daniel C. Nelson and Julia Garbe and Mattias Collin},
  booktitle={Biological chemistry},
  year={2011}
}
Abstract Group A streptococcus (Streptococcus pyogenes) is an exclusively human pathogen that causes a wide spectrum of diseases ranging from pharyngitis, to impetigo, to toxic shock, to necrotizing fasciitis. The diversity of these disease states necessitates that S. pyogenes possess the ability to modulate both the innate and adaptive immune responses. SpeB, a cysteine proteinase, is the predominant secreted protein from S. pyogenes. Because of its relatively indiscriminant specificity, this… 

An irreversible inhibitor to probe the role of Streptococcus pyogenes cysteine protease SpeB in evasion of host complement defenses.

TLDR
2S-alkyne is developed and characterize a clickable inhibitor of Streptococcal pyrogenic exotoxin B that reduces S. pyogenes survival in the presence of human neutrophils and supports the role of SpeB-mediated proteolysis as a mechanism to limit complement-mediated host defense.

The Streptococcal Cysteine Protease SpeB Is Not a Natural Immunoglobulin-Cleaving Enzyme

TLDR
It is shown that SpeB has no Ig-cleaving activity under physiological conditions and that only Igs in a reduced state, i.e., semimonomeric molecules, are cleaved and degraded by SpeB.

A Puzzling Promiscuous Protease: Role of the Streptococcal SpeB Protein in Host Virulence and Polymicrobial Dynamics

TLDR
The findings do not support a role for SpeB in the virulence of AP53CovS+ GAS in models of skin and subcutaneous infection, and it is demonstrated that SpeB exhibits potent biofilm disruption activity at multiple stages of S. aureus biofilm formation.

The Streptococcal Protease SpeB Antagonizes the Biofilms of the Human Pathogen Staphylococcus aureus USA300 through Cleavage of the Staphylococcal SdrC Protein

TLDR
The demonstration that SpeB can degrade the biofilms of the human pathogen Staphylococcus aureus has important implications for how SpeB may be utilized by GAS to successfully compete in a polymicrobial environment.

Molecular and genomic characterization of pathogenic traits of group A Streptococcus pyogenes

TLDR
Some important cellular and extracellular substances that may affect pathogenic processes during GAS infections, and the host responses to these are summarized.

Proteolytic Profiling of Streptococcal Pyrogenic Exotoxin B (SpeB) by Complementary HPLC-MS Approaches

TLDR
This study precisely depicts the proteolytic properties of SpeB and provides a library of potential host substrates, including their exact cleavage positions, as a valuable source for further research to unravel the role of Spe B during streptococcal infection.

Metal-Mediated Modulation of Streptococcal Cysteine Protease Activity and Its Biological Implications

TLDR
It is proposed that zinc and/or copper availability in the bacterial microenvironment can modulate the proteolytic activity of SpeB in a manner that preserves the integrity of several other virulence factors essential for bacterial survival and dissemination within the host and thereby may exacerbate the severity of invasive GAS infections.

Group A Streptococcal Cysteine Protease Cleaves Epithelial Junctions and Contributes to Bacterial Translocation*

TLDR
Findings indicate that the proteolytic efficacy of SpeB in junctional degradation allows GAS to invade deeper into tissues.

Endopeptidase PepO Regulates the SpeB Cysteine Protease and Is Essential for the Virulence of Invasive M1T1 Streptococcus pyogenes

TLDR
The results expand the complex regulatory network that is operating in GAS to control SpeB production and suggest that PepO is a virulence requirement during GAS M1T1 strain 5448 infections.
...

References

SHOWING 1-10 OF 106 REFERENCES

Streptococcal Cysteine Proteinase Releases Biologically Active Fragments of Streptococcal Surface Proteins (*)

TLDR
In these serious complications to S. pyogenes infections immune complexes are found in affected organs, and removal of this and other surface proteins could promote bacterial dissemination, whereas the generation of soluble complexes between Immunoglobulins and immunoglobulin-binding streptococcalsurface proteins could be an etiological factor in the development of glomerulonephritis and rheumatic fever.

The SpeB virulence factor of Streptococcus pyogenes, a multifunctional secreted and cell surface molecule with strepadhesin, laminin‐binding and cysteine protease activity

TLDR
This work identifies strepadhesin, a novel glycoprotein‐binding activity in Streptococcus pyogenes, which is regulated by Mga, a regulator of streptococcal virulence factors, and finds that it is carried by SpeB, strethococcal pyrogenic exotoxin with cysteine protease activity.

EndoS, a novel secreted protein from Streptococcus pyogenes with endoglycosidase activity on human IgG

TLDR
This report shows that S.pyogenes has the ability to hydrolyze the chitobiose core of the asparagine‐linked glycan on immuno globulin G (IgG) when bacteria are grown in the presence of human plasma, and reveals a novel mechanism which may contribute to S. pyogenes pathogenesis.

Crystal structure of the zymogen form of the group A Streptococcus virulence factor SpeB: an integrin-binding cysteine protease.

TLDR
The crystal structure of streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that is a major virulence factor of the human pathogen Streptococcus pyogenes and participates in invasive disease episodes, is determined.

Genetic Inactivation of an Extracellular Cysteine Protease (SpeB) Expressed by Streptococcus pyogenes Decreases Resistance to Phagocytosis and Dissemination to Organs

TLDR
Results indicate that genetic inactivation of the cysteine protease decreased the resistance of the mutant to phagocytosis and impaired its subsequent dissemination to organs, providing insight into the detrimental effect of SpeB inactivation on virulence.

Purification and Characterization of a Novel Cysteine Proteinase (Periodontain) from Porphyromonas gingivalis

TLDR
The presence of this enzyme, which rapidly inactivates α1-proteinase inhibitor, could result in elevated levels of human neutrophil elastase clinically detected in periodontal disease and should be considered as a potential virulence factor for P. gingivalis.

A conserved Streptococcus pyogenes extracellular cysteine protease cleaves human fibronectin and degrades vitronectin.

TLDR
The results demonstrate that the cysteine protease is well conserved in natural populations of S. pyogenes, provide additional evidence that this enzyme is involved in host-parasite interactions, and suggest that the protease plays a role in bacterial dissemination, colonization, and invasion, and inhibition of wound healing.

Inactivation of the cysteine protease SpeB affects hyaluronic acid capsule expression in group A streptococci.

TLDR
A strain-dependent decrease of hyaluronic acid capsule production and an increase in superoxide dismutase transcription are revealed in the Streptococcal pyrogenic exotoxin A strain.

Streptococcal cysteine proteinase releases kinins: a virulence mechanism

TLDR
It is found that the purified streptococcal cysteine proteinase releases biologically active kinins from their purified precursor protein, H-kininogen, in vitro, and from kininogens present in the human plasma, ex vivo.

Streptococcal Mitogenic Exotoxin, SmeZ, Is the Most Susceptible M1T1 Streptococcal Superantigen to Degradation by the Streptococcal Cysteine Protease, SpeB*

TLDR
The study provides evidence for the effect of subtle structural differences between highly similar SAgs on their biological activity and demonstrates that the order of susceptibility of the M1T1 S Ags to SpeB proteolysis is unaltered when they are present in a mixture that reflects their native physiological status.
...