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

被引:49
作者
Alharthi, Sitah [1 ,2 ]
Alavi, Seyed Ebrahim [1 ]
Moyle, Peter Michael [1 ]
Ziora, Zyta Maria [3 ]
机构
[1] Univ Queensland, Sch Pharm, Woolloongabba, Qld 4102, Australia
[2] Shaqra Univ, Sch Pharm, Dept Pharmaceut Sci, Riyadh, Saudi Arabia
[3] Univ Queensland, Inst Mol Biosci, St Lucia, Qld 4067, Australia
关键词
Antimicrobial resistance; Anti-virulence therapy; Gram-positive bacteria; Sortase A inhibitors; Virulence factors; STREPTOCOCCUS-MUTANS SORTASE; ANTIMICROBIAL PEPTIDES; ANTIBACTERIAL ACTIVITY; NATURAL-PRODUCTS; AUREUS SORTASE; VIRULENCE; RESISTANCE; OPTIMIZATION; ANTIBIOTICS; COMBINATION;
D O I
10.1016/j.drudis.2021.03.019
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:2164 / 2172
页数:9
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