Sortase A Inhibition: Updated Review of Non-Peptide Ligands for Targeting Staphylococcus Aureus Virulence

Sortases are a class of bacterial enzymes that are responsible for altering surface proteins and supporting attachment to host cells and enhancing biofilm formation, which poses resistance to the anti-virulence therapy. These enzymes are found in Gram-positive bacteria and can be classified into classes A-F. Sortase A, found in Staphylococcus aureus, is the prototype member of the sortase family and acts as the pioneer to study the working mechanism, applications, and structure of sortases. Sortases attract the attention of researchers as a target for the development of inhibitors used for anti-virulence therapy. Prevention of formation of biofilm is challenging, and hence is targeted using Gram-positive bacteria containing sortase A. In this review, sortase inhibitors are categorized on the basis of specific chemical features such as vinyl sulfone, anthraquinones, isoquinoline derivatives, indoles, pyrrolomycins, thiadiazoles, natural variants, and so on. Further research on sortase in search of inhibitors continues in order to create a new class of anti-infective drugs suitable for humans to prevent the dreadful rise of antimicrobial resistance.