Sortase A (SrtA)

Sortase A is a membrane-associated cysteine transpeptidase found predominantly in Gram-positive bacteria such as *Staphylococcus aureus*. It catalyzes the covalent anchoring of specific surface proteins containing an LPXTG motif to the peptidoglycan layer of the bacterial cell wall. The enzyme recognizes this sorting signal at protein C termini, cleaves between threonine and glycine residues within this motif using its active-site cysteine thiol group, forms an acyl-enzyme intermediate with threonine’s carboxyl group, then resolves this intermediate via nucleophilic attack from amino groups on lipid II precursors—ultimately linking proteins to peptidoglycan. This process is essential for displaying many virulence factors required for host colonization and infection. Because it plays a central role in pathogenesis but is not required for bacterial viability under all conditions, Sortase A has emerged as an attractive target for antivirulence therapies designed to disarm rather than kill pathogenic bacteria.

Other names

SrtAStaphylococcus aureus sortase AHousekeeping sortase

Drugs or inhibitors targeting Sortase A typically act by blocking its active site cysteine residue or interfering with substrate binding, thereby preventing covalent attachment of virulence factors to the cell wall. This disrupts bacterial colonization without necessarily killing bacteria directly ("anti-infective" or "antivirulence" mechanism).