Next Article in Journal
Molecular Targeted Therapies for the Treatment of Leptomeningeal Carcinomatosis: Current Evidence and Future Directions
Next Article in Special Issue
Non-Classical Inhibition of Carbonic Anhydrase
Previous Article in Journal
Diet Quality and Cancer Outcomes in Adults: A Systematic Review of Epidemiological Studies
Previous Article in Special Issue
Structure and Functional Diversity of GCN5-Related N-Acetyltransferases (GNAT)
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(7), 1072; doi:10.3390/ijms17071072

Staphylococcal Superantigen-Like Protein 1 and 5 (SSL1 & SSL5) Limit Neutrophil Chemotaxis and Migration through MMP-Inhibition

Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
*
Author to whom correspondence should be addressed.
Academic Editor: Claudiu T. Supuran
Received: 30 May 2016 / Revised: 27 June 2016 / Accepted: 28 June 2016 / Published: 5 July 2016
(This article belongs to the Special Issue Enzyme-Inhibitor Interaction as Examples of Molecular Recognition)
View Full-Text   |   Download PDF [1977 KB, uploaded 5 July 2016]   |  

Abstract

Matrix metalloproteinases (MMPs) are endopeptidases that degrade components of the extracellular matrix, but also modulate inflammation. During bacterial infections, MMPs are important in the recruitment and migration of inflammatory cells. Besides facilitating cell migration by degrading extracellular matrix components, they potentiate the action of several inflammatory molecules, including cytokines, chemokines, and antimicrobial peptides. Staphylococcus aureus secretes an arsenal of immune evasion molecules that interfere with immune cell functioning and hamper proper immune responses. An earlier study identified staphylococcal superantigen-like protein 5 (SSL5) as an MMP9 inhibitor. Since multiple MMPs are involved in neutrophil recruitment, we set up an in-depth search for additional MMP inhibitors by testing a panel of over 70 secreted staphylococcal proteins on the inhibition of the two main neutrophil MMPs: MMP8 (neutrophil collagenase) and MMP9 (neutrophil gelatinase B). We identified SSL1 and SSL5 as potent inhibitors of both neutrophil MMPs and show that they are actually broad range MMP inhibitors. SSL1 and SSL5 prevent MMP-induced cleavage and potentiation of IL-8 and inhibit the migration of neutrophils through collagen. Thus, through MMP-inhibition, SSL1 and SSL5 interfere with neutrophil activation, chemotaxis, and migration, all vital neutrophil functions in bacterial clearance. Studies on MMP-SSL interactions can have therapeutic potential and SSL based derivatives might prove useful in treatment of cancer and destructive inflammatory diseases. View Full-Text
Keywords: S. aureus; immune evasion; matrix metalloproteinase; enzyme-inhibitor; neutrophil; innate immunity; staphylococcal superantigen-like proteins S. aureus; immune evasion; matrix metalloproteinase; enzyme-inhibitor; neutrophil; innate immunity; staphylococcal superantigen-like proteins
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Koymans, K.J.; Bisschop, A.; Vughs, M.M.; van Kessel, K.P.M.; de Haas, C.J.C.; van Strijp, J.A.G. Staphylococcal Superantigen-Like Protein 1 and 5 (SSL1 & SSL5) Limit Neutrophil Chemotaxis and Migration through MMP-Inhibition. Int. J. Mol. Sci. 2016, 17, 1072.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top