Sortase A (SrtA) inhibitors as an alternative treatment for superbug infections

Sitah Alharthi; Seyed Ebrahim Alavi; Peter Michael Moyle; Zyta Maria Ziora

doi:10.1016/j.drudis.2021.03.019

Sortase A (SrtA) inhibitors as an alternative treatment for superbug infections

Sitah Alharthi, Seyed Ebrahim Alavi, Peter Michael Moyle, Zyta Maria Ziora

Western Sydney University

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

Abstract

Virulence factor, sortase A (SrtA), has crucial roles in the pathogenesis of Gram-positive superbugs. SrtAis 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.

Original language	English
Pages (from-to)	2164-2172
Number of pages	9
Journal	Drug Discovery Today
Volume	26
Issue number	9
DOIs	https://doi.org/10.1016/j.drudis.2021.03.019
Publication status	Published - 2021

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10.1016/j.drudis.2021.03.019

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title = "Sortase A (SrtA) inhibitors as an alternative treatment for superbug infections",

abstract = "Virulence factor, sortase A (SrtA), has crucial roles in the pathogenesis of Gram-positive superbugs. SrtAis 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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AU - Moyle, Peter Michael

AU - Ziora, Zyta Maria

PY - 2021

Y1 - 2021

N2 - Virulence factor, sortase A (SrtA), has crucial roles in the pathogenesis of Gram-positive superbugs. SrtAis 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.

AB - Virulence factor, sortase A (SrtA), has crucial roles in the pathogenesis of Gram-positive superbugs. SrtAis 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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VL - 26

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EP - 2172

JO - Drug Discovery Today

JF - Drug Discovery Today

IS - 9

ER -

Sortase A (SrtA) inhibitors as an alternative treatment for superbug infections

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