Title: Evaluation of the type I signal peptidase as antibacterial target for biofilm-associated infections of Staphylococcus epidermidis
Authors: Bockstael, Katrijn
Geukens, Nick
Van Mellaert, Lieve
Herdewijn, Piet
Anné, Jozef
Van Aerschot, Arthur # ×
Issue Date: Nov-2009
Publisher: Society for General Microbiology
Series Title: Microbiology-SGM vol:155 pages:3719-3729
Abstract: The development of antibacterial resistance is inevitable and is a major concern in hospitals and communities. Moreover, biofilm-grown bacteria are less sensitive to antimicrobial treatment. In this respect, the Gram-positive Staphylococcus epidermidis is an important source of nosocomial biofilm-associated infections. In the search for new antibacterial therapies, the type I signal peptidase (SPase I) serves as a potential target for development of antibacterials with a novel mode of action. This enzyme cleaves off the signal peptide from secreted proteins, making it essential for protein secretion, and hence for bacterial cell viability. S. epidermidis encodes three putative SPases I (denoted Sip1, Sip2 and Sip3), of which Sip1 lacks the catalytic lysine. In this report, we investigated the active S. epidermidis SPases I in more detail. Sip2 and Sip3 were found to complement a temperature-sensitive Escherichia coli lepB mutant, demonstrating their in vivo functional activity. In vitro functional activity of purified Sip2 and Sip3 proteins and inhibition of their activity by the SPase I inhibitor arylomycin A2 were further illustrated using a fluorescence resonance energy transfer (FRET)-based assay. Furthermore, we demonstrated that SPase I not only is an attractive target for development of novel antibacterials against free-living bacteria, but also is a feasible target for biofilm-associated infections.
ISSN: 1350-0872
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Medicinal Chemistry (Rega Institute)
Laboratory of Molecular Bacteriology (Rega Institute)
Chemistry, Campus Kulak Kortrijk
Laboratory for the Research of Neurodegenerative Diseases (VIB-KU Leuven Center for Brain & Disease Research)
× corresponding author
# (joint) last author

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