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Clinical Microbiology Reviews, April 2009, p. 224-239, Vol. 22, No. 2
0893-8512/09/$08.00+0     doi:10.1128/CMR.00047-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Matrix Metalloproteinases as Drug Targets in Infections Caused by Gram-Negative Bacteria and in Septic Shock

Ineke Vanlaere and Claude Libert* Author Bios

Department for Molecular Biomedical Research, VIB, B-9052 Ghent, Belgium, and Department of Molecular Biology, Ghent University, B-9052 Ghent, Belgium

Summary: The mammalian immune system is optimized to cope effectively with the constant threat of pathogens. However, when the immune system overreacts, sepsis, severe sepsis, or septic shock can develop. Despite extensive research, these conditions remain the leading cause of death in intensive care units. The matrix metalloproteinases (MMPs) constitute a family of proteases that are expressed in developmental, physiological, and pathological processes and also in response to infections. Studies using MMP inhibitors and MMP knockout mice indicate that MMPs play essential roles in infection and in the host defense against infection. This review provides a brief introduction to some basic concepts of infections caused by gram-negative bacteria and reviews reports describing MMP expression and inhibition, as well as studies with MMP-deficient mice in models of infection caused by gram-negative bacteria and of septic shock. We discuss whether MMPs should be considered novel drug targets in infection and septic shock.

* Corresponding author. Mailing address: DMBR, VIB & Ghent University, Technologiepark 927, B-9052 Ghent (Zwijnaarde), Belgium. Phone: 32-9-3313700. Fax: 32-9-3313609. E-mail: Claude.Libert{at}dmbr.vib-UGent.be

Clinical Microbiology Reviews, April 2009, p. 224-239, Vol. 22, No. 2
0893-8512/09/$08.00+0     doi:10.1128/CMR.00047-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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