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

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Sortase A is a membrane enzyme responsible for the anchoring of surface-exposed proteins to the cellwall envelope of Gram-positive bacteria. As a well-studied member of the sortase subfamily catalysingthe cell wall anchoring of important virulence factors to the surface of staphylococci, enterococci andstreptococci, sortase A plays a critical role in Gram-positive bacterial pathogenesis. It is thus considered apromising target for the development of new anti-infective drugs that aim to interfere with importantGram-positive virulence mechanisms, such as adhesion to host tissues, evasion of host defences, andbiofilm 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 itmore accessible to inhibitor targeting, constitute additional reasons reinforcing the view that sortase A isan ideal target for anti-virulence drug development. Many inhibitors of sortase A have been identified todate using high-throughput orin silicoscreening of compound libraries (synthetic or natural), and whilemany have proved useful tools for probing the action model of the enzyme, several are also promisingcandidates for the development into potent inhibitors. This review is focused on the most promisingsortase 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 antimicrobialresistance.
Lingua originaleEnglish
Numero di pagine7
RivistaMicrobial Pathogenesis
Stato di pubblicazionePublished - 2014

All Science Journal Classification (ASJC) codes

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