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Sortase A (SrtA) inhibitors as an alternative treatment for superbug infections
Sitah Alharthi1, Seyed Ebrahim Alavi2, Peter Michael Moyle2
1School of Pharmacy, The University of Queensland, Woolloongabba, Qld 4102, Australia; Department of Pharmaceutical Science, School of Pharmacy, Shaqra University, Riyadh, Saudi Arabia.
Abstract:
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.
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