Down-regulation of human extracellular cysteine protease inhibitors by the secreted staphylococcal cysteine proteases, staphopain A and B.
Vincents, Bjarne LU ; Önnerfjord, Patrik LU
; Gruca, Milosz
; Potempa, Jan
and Abrahamson, Magnus
LU
(2007)
In Biological Chemistry
388(4).
p.437-446
- Abstract
- Of seven human cystatins investigated, none inhibited the cysteine proteases staphopain A and B secreted by the human pathogen Staphylococcus aureus. Rather, the extracellular cystatins C, D and E/M were hydrolyzed by both staphopains. Based on MALDI-TOF time-course experiments, staphopain A cleavage of cystatin C and D should be physiologically relevant and occur upon S. aureus infection. Staphopain A hydrolyzed the Glyl 1 bond of cystatin C and the Ala10 bond of cystatin D with similar K-m values of approximately 33 and 32 mu m, respectively. Such N-terminal truncation of cystatin C caused > 300-fold lower inhibition of papain, cathepsin B, L and K, whereas the cathepsin H activity was compromised by a factor of ca. 10. Similarly,... (More)
- Of seven human cystatins investigated, none inhibited the cysteine proteases staphopain A and B secreted by the human pathogen Staphylococcus aureus. Rather, the extracellular cystatins C, D and E/M were hydrolyzed by both staphopains. Based on MALDI-TOF time-course experiments, staphopain A cleavage of cystatin C and D should be physiologically relevant and occur upon S. aureus infection. Staphopain A hydrolyzed the Glyl 1 bond of cystatin C and the Ala10 bond of cystatin D with similar K-m values of approximately 33 and 32 mu m, respectively. Such N-terminal truncation of cystatin C caused > 300-fold lower inhibition of papain, cathepsin B, L and K, whereas the cathepsin H activity was compromised by a factor of ca. 10. Similarly, truncation of cystatin D caused alleviated inhibition of all endogenous target enzymes investigated. The normal activity of the cystatins is thus down-regulated, indicating that the bacterial enzymes can cause disturbance of the host protease-inhibitor balance. To illustrate the in vivo consequences, a mixed cystatin C assay showed release of cathepsin B activity in the presence of staphopain A. Results presented for the specificity of staphopains when interacting with cystatins as natural protein substrates could aid in the development of therapeutic agents directed toward these proteolytic virulence factors. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/166183
- author
- Vincents, Bjarne
LU
; Önnerfjord, Patrik
LU
; Gruca, Milosz
; Potempa, Jan
and Abrahamson, Magnus
LU
- organization
- publishing date
- 2007
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- protease inhibitors, cysteine peptidases, Staphylococcus aureus, virulence factors
- in
- Biological Chemistry
- volume
- 388
- issue
- 4
- pages
- 437 - 446
- publisher
- De Gruyter
- external identifiers
-
- wos:000245407000010
- scopus:34047095311
- ISSN
- 1437-4315
- DOI
- 10.1515/BC.2007.042
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Division of Clinical Chemistry and Pharmacology (013250300), Connective Tissue Biology (013230151)
- id
- 56289f04-9a3a-414f-b858-3a0cd5104f60 (old id 166183)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17391065&dopt=Abstract
- date added to LUP
- 2016-04-01 12:15:56
- date last changed
- 2022-01-27 01:12:01
@article{56289f04-9a3a-414f-b858-3a0cd5104f60,
abstract = {{Of seven human cystatins investigated, none inhibited the cysteine proteases staphopain A and B secreted by the human pathogen Staphylococcus aureus. Rather, the extracellular cystatins C, D and E/M were hydrolyzed by both staphopains. Based on MALDI-TOF time-course experiments, staphopain A cleavage of cystatin C and D should be physiologically relevant and occur upon S. aureus infection. Staphopain A hydrolyzed the Glyl 1 bond of cystatin C and the Ala10 bond of cystatin D with similar K-m values of approximately 33 and 32 mu m, respectively. Such N-terminal truncation of cystatin C caused > 300-fold lower inhibition of papain, cathepsin B, L and K, whereas the cathepsin H activity was compromised by a factor of ca. 10. Similarly, truncation of cystatin D caused alleviated inhibition of all endogenous target enzymes investigated. The normal activity of the cystatins is thus down-regulated, indicating that the bacterial enzymes can cause disturbance of the host protease-inhibitor balance. To illustrate the in vivo consequences, a mixed cystatin C assay showed release of cathepsin B activity in the presence of staphopain A. Results presented for the specificity of staphopains when interacting with cystatins as natural protein substrates could aid in the development of therapeutic agents directed toward these proteolytic virulence factors.}},
author = {{Vincents, Bjarne and Önnerfjord, Patrik and Gruca, Milosz and Potempa, Jan and Abrahamson, Magnus}},
issn = {{1437-4315}},
keywords = {{protease inhibitors; cysteine peptidases; Staphylococcus aureus; virulence factors}},
language = {{eng}},
number = {{4}},
pages = {{437--446}},
publisher = {{De Gruyter}},
series = {{Biological Chemistry}},
title = {{Down-regulation of human extracellular cysteine protease inhibitors by the secreted staphylococcal cysteine proteases, staphopain A and B.}},
url = {{http://dx.doi.org/10.1515/BC.2007.042}},
doi = {{10.1515/BC.2007.042}},
volume = {{388}},
year = {{2007}},
}