Identification of Sortase

BACKGROUND: Hospital-borne bacterial infections present a major challenge in patient care due to the rising number of strains resistant to multiple antibiotics in recent years. Gram-positive bacteria, such as Staphylococci, Streptococci and Pneumococci, are the most common cause of these often fatal infections and are particularly more difficult to treat in immunocompromised patients. Therefore, there is an urgent need for identifying novel targets sites in these pathogens for the development of antibiotics.

A unique characteristic of these pathogens, including Staphylococci, is the presence of surface proteins anchored to the cell wall, many of which are essential for pathogenesis. The anchoring process involves secretion of the protein through the cellular membrane, followed by its cleavage at a C-terminal sorting signal and anchoring of the cleaved protein to the cell wall peptidoglycan. This two-step transpeptidation reaction is catalyzed by the enzyme sortase. Since these final processes catalyzed by sortase are crucial in the presentation of biologically active surface proteins and the enzyme is conserved in gram positive bacteria but absent in humans, sortase is an attractive novel target for the development of effective and safe antibiotics directed towards many gram positive pathogenic bacteria.

DESCRIPTION: Researchers at the University of California have identified a novel sortase (Sortase B; SrtB) in Staphylococcus aureus. SrtB is a cysteine transpeptidase, similar to a previously discovered sortase, SrtA, and has the ability to cleave surface destined proteins bearing a sorting signal motif as well as to cross-link it to the cell wall peptidoglycan. The UC researchers further describe methods for purification of srtB and its potential uses in various screening and detection applications.

ADVANTAGES:

* Novel target for development of antibiotic therapeutics.
* Conserved structure facilitates design of drugs for broader class of gram-positive bacterial pathogens.
* Availability of gene facilitates production of recombinant protein for preparation of antibodies and other research purposes.

APPLICATIONS:

* Design and screening of chemical inhibitors of sortase-mediated transpeptidase activity.
* Use of cell wall surface sorted molecules such as antibodies or detection reagents for the treatment and diagnosis of bacterial infections.
* For protein and peptide display on bacterial surfaces for use in protein/peptide display libraries and vaccine production
* For screening expression library of clones expressing desired protein.

REFERENCE: 1999-262

Patents:
US 7,101,692   [MORE INFO]

Type of Offer: Licensing



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