scholarly journals The M Protein Is Dispensable for Maturation of Streptococcal Cysteine Protease SpeB

2005 ◽  
Vol 73 (2) ◽  
pp. 859-864 ◽  
Author(s):  
Björn Zimmerlein ◽  
Hae-Sun Park ◽  
Shaoying Li ◽  
Andreas Podbielski ◽  
P. Patrick Cleary
Keyword(s):  
Cysteine Protease ◽  
Protease Activity ◽  
Active Form ◽  
Surface Protein ◽  
M Protein ◽  
Cysteine Protease Activity ◽  
Group A ◽  
Streptococcal Pyrogenic Exotoxin B ◽  
Major Surface ◽  
Culture Supernatants

ABSTRACT The streptococcal pyrogenic exotoxin B (SpeB) is an important virulence factor of group A streptococci (GAS) with cysteine protease activity. Maturation of SpeB to a proteolytically active form was suggested to be dependent on cell-wall-anchored M1 protein, the major surface protein of GAS (M. Collin and A. Olsén, Mol. Microbiol. 36:1306-1318, 2000). Collin and Olsén showed that mutant GAS strains expressing truncated M protein secrete a conformationally different form of unprocessed SpeB with no proteolytic activity. Alternatively, we hypothesized that a truncated M protein may interfere with processing of this secreted protease, and therefore we tested cysteine protease activity in genetically defined mutant strains that express either no M protein or membrane-anchored M protein with an in-frame deletion of the AB repeat region. Measurements of SpeB activity by cleavage of a substrate n-benzoyl-Pro-Phe-Arg-p-nitroanilide hydrochloride showed that the proteolytic activities in culture supernatants of both mutants were similar to those from the wild-type strain. In addition, Western blot analysis of culture supernatants showed that SpeB expression and processing to a mature form was unaffected by either deletion mutation. Therefore, we conclude that M protein is not required for maturation of the streptococcal cysteine protease SpeB.

scholarly journals Inverse Relation between Disease Severity and Expression of the Streptococcal Cysteine Protease, SpeB, among Clonal M1T1 Isolates Recovered from Invasive Group A Streptococcal Infection Cases

2000 ◽  
Vol 68 (11) ◽  
pp. 6362-6369 ◽  
Author(s):  
Rita G. Kansal ◽  
Allison McGeer ◽  
Donald E. Low ◽  
Anna Norrby-Teglund ◽  
Malak Kotb
Keyword(s):  
Cysteine Protease ◽  
Protease Activity ◽  
Invasive Disease ◽  
M Protein ◽  
Streptococcal Toxic Shock Syndrome ◽  
Invasive Infection ◽  
Cysteine Protease Activity ◽  
Invasive Infections ◽  
Group A ◽  
High Degree

ABSTRACT The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) cases. The expression and amount of the 28-kDa SpeB protein produced were determined by quantitative Western blotting, and protease activity was measured by a fluorescent enzymatic assay. A high degree of variation in SpeB expression was seen among the isolates, and this variation seemed to correlate with the severity and/or clinical manifestation of the invasive infection. The mean amount of 28-kDa SpeB protein and cysteine protease activity produced by isolates from nonsevere cases was significantly higher than that from STSS cases (P = 0.001). This difference was partly due to the fact that 41% of STSS isolates produced little or no SpeB compared to only 14% of isolates recovered in nonsevere cases. Moreover, the cysteine protease activity among those isolates that expressed SpeB was significantly lower for STSS isolates than for isolates from nonsevere cases (P = 0.001). Increased SpeB production was also inversely correlated with intact M protein expression, and inhibition of cysteine protease activity blocked the cleavage of the surface M protein. Together, the data support the existence of both an “on-off” and a posttranslational regulatory mechanism(s) controlling SpeB production, and they suggest that isolates with the speB gene in the “off” state are more likely to spare the surface M protein and to be isolated from cases of severe rather than nonsevere invasive infection. These findings may have important implications for the role of SpeB in host-pathogen interactions via regulation of the expression of GAS virulence genes and the severity of invasive disease.

scholarly journals Cysteine protease activity in the wall of abdominal aortic aneurysms

2007 ◽  
Vol 46 (6) ◽  
pp. 1260-1266 ◽  
Author(s):  
Said Abisi ◽  
Kevin G. Burnand ◽  
Matthew Waltham ◽  
Julia Humphries ◽  
Peter R. Taylor ◽  
...  
Keyword(s):  
Cysteine Protease ◽  
Protease Activity ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Cysteine Protease Activity ◽  
Abdominal Aortic

scholarly journals Epicutaneous Administration of Papain Induces IgE and IgG Responses in a Cysteine Protease Activity-Dependent Manner

2014 ◽  
Vol 63 (2) ◽  
pp. 219-226 ◽  
Author(s):  
Hideo Iida ◽  
Toshiro Takai ◽  
Yusuke Hirasawa ◽  
Seiji Kamijo ◽  
Sakiko Shimura ◽  
...  
Keyword(s):  
Cysteine Protease ◽  
Protease Activity ◽  
Dependent Manner ◽  
Cysteine Protease Activity ◽  
Activity Dependent

Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes

2007 ◽  
Vol 3 (10) ◽  
pp. 668-677 ◽  
Author(s):  
Galia Blum ◽  
Georges von Degenfeld ◽  
Milton J Merchant ◽  
Helen M Blau ◽  
Matthew Bogyo
Keyword(s):  
Optical Imaging ◽  
Cysteine Protease ◽  
Protease Activity ◽  
Cysteine Protease Activity

Elevetad Cysteine-Protease Activity in Bronchiolitis Obliterans Syndrome

2019 ◽  
Vol 38 (4) ◽  
pp. S250
Author(s):  
C. Morrone ◽  
N. Smirnova ◽  
N. Kneidinger ◽  
H. Schiller ◽  
O. Eickelberg ◽  
...  
Keyword(s):  
Cysteine Protease ◽  
Protease Activity ◽  
Bronchiolitis Obliterans ◽  
Bronchiolitis Obliterans Syndrome ◽  
Cysteine Protease Activity

Inhibition of cathepsin B reduces β-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate β-secretase of Alzheimer's disease

2005 ◽  
Vol 386 (9) ◽  
Author(s):  
Vivian Hook ◽  
Thomas Toneff ◽  
Matthew Bogyo ◽  
Doron Greenbaum ◽  
Katalin F. Medzihradszky ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cysteine Protease ◽  
Cathepsin B ◽  
Protease Activity ◽  
Chromaffin Cells ◽  
Secretory Pathway ◽  
Secretory Vesicles ◽  
Cysteine Protease Activity ◽  
Regulated Secretory Pathway

AbstractThe regulated secretory pathway of neurons is the major source of extracellular Aβ that accumulates in Alzheimer's disease (AD). Extracellular Aβ secreted from that pathway is generated by β-secretase processing of amyloid precursor protein (APP). Previously, cysteine protease activity was demonstrated as the major β-secretase activity in regulated secretory vesicles of neuronal chromaffin cells. In this study, the representative cysteine protease activity in these secretory vesicles was purified and identified as cathepsin B by peptide sequencing. Immunoelectron microscopy demonstrated colocalization of cathepsin B with Aβ in these vesicles. The selective cathepsin B inhibitor, CA074, blocked the conversion of endogenous APP to Aβ in isolated regulated secretory vesicles. In chromaffin cells, CA074Me (a cell permeable form of CA074) reduced by about 50% the extracellular Aβ released by the regulated secretory pathway, but CA074Me had no effect on Aβ released by the constitutive pathway. Furthermore, CA074Me inhibited processing of APP into the COOH-terminal β-secretase-like cleavage product. These results provide evidence for cathepsin B as a candidate β-secretase in regulated secretory vesicles of neuronal chromaffin cells. These findings implicate cathepsin B as β-secretase in the regulated secretory pathway of brain neurons, suggesting that inhibitors of cathepsin B may be considered as therapeutic agents to reduce Aβ in AD.

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