Sortase A : an ideal target for anti-virulence drug development

Cascioferro, Stella, Totsika, Makrina, & Schillaci, Domenico (2014) Sortase A : an ideal target for anti-virulence drug development. Microbial Pathogenesis, 77, pp. 105-112.

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Abstract

Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cell wall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysing the cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci and streptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered a promising target for the development of new anti-infective drugs that aim to interfere with important Gram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, and biofilm formation. The additional properties of sortase A as an enzyme that is not required for Gram-positive bacterial growth or viability and is conveniently located on the cell membrane making it more accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A is an ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified to date using high-throughput or in silico screening of compound libraries (synthetic or natural), and while many have proved useful tools for probing the action model of the enzyme, several are also promising candidates for the development into potent inhibitors. This review is focused on the most promising sortase A inhibitor compounds that are currently in development as leads towards a new class of anti-infective drugs that are urgently needed to help combat the alarming increase in antimicrobial resistance.

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ID Code: 79637
Item Type: Journal Article
Refereed: Yes
Keywords: Sortase A, Sortase A inhibitors, Antivirulence drugs, Gram-positive pathogens, Antimicrobial resistance
DOI: 10.1016/j.micpath.2014.10.007
ISSN: 0882-4010
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2014 Elsevier Ltd.
Copyright Statement: NOTICE: this is the author’s version of a work that was accepted for publication in Microbial Pathogenesis. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Microbial Pathogenesis, Volume 77, (December 2014), DOI: 10.1016/j.micpath.2014.10.007
Deposited On: 23 Dec 2014 04:33
Last Modified: 04 Jan 2016 11:34

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