Abstract
•Superbugs are one of the most serious threats to human and veterinary health.•Sortase A is a virulence factor present in the cell wall Gram-positive bacteria.•Sortase A inhibition is a promising approach to overcome antimicrobial resistance.•Sortase A inhibitors can hinder the development of side effects associated with antibiotics.
Virulence factor, sortase A (SrtA), has crucial roles in the pathogenesis of Gram-positive superbugs. SrtA is a bacterial cell membrane enzyme that anchors crucial virulence factors to the cell wall surface of Gram-positive bacteria. SrtA is not necessary for bacterial growth and viability and is conveniently accessible in the cell membrane; therefore, it is an ideal target for antivirulence drug development. In this review, we focus on antimicrobial resistance (AMR)-expressing bacteria and SrtA as a potential target for overcoming AMR. The mechanism of action of SrtA and its inhibition by various types of inhibitors, such as synthetic small molecules, peptides, and natural products, are provided. Future SrtA research perspectives for alternative drug development to antibiotics are also proposed.