School of Pharmacy, The University of Queensland, Woolloongabba, Qld 4102, Australia; Department of Pharmaceutical Science, School of Pharmacy, Shaqra University, Riyadh, Saudi Arabia.
School of Pharmacy, The University of Queensland, Woolloongabba, Qld 4102, Australia.
Drug Discov Today. 2021 Sep;26(9):2164-2172. doi: 10.1016/j.drudis.2021.03.019. Epub 2021 Mar 27.
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.
毒力因子,即 sortase A(SrtA),在革兰氏阳性超级细菌的发病机制中起着至关重要的作用。SrtA 是一种细菌细胞膜酶,可将关键的毒力因子锚定在革兰氏阳性菌的细胞壁表面。SrtA 对于细菌的生长和活力并非必需,并且在细胞膜中易于获得;因此,它是抗毒力药物开发的理想靶标。在本综述中,我们重点关注表达抗菌药物耐药性(AMR)的细菌和 SrtA 作为克服 AMR 的潜在靶标。提供了 SrtA 的作用机制及其被各种类型抑制剂(如合成小分子、肽和天然产物)抑制的机制。还提出了未来 SrtA 研究替代抗生素药物开发的前景。