Departamento de Biologia Molecular, Centro de Ciências Exatas e da Natureza, Universidade Federal da Paraíba, Paraíba, Brazil.
Biochim Biophys Acta Proteins Proteom. 2022 May 1;1870(5):140782. doi: 10.1016/j.bbapap.2022.140782. Epub 2022 Apr 22.
Protein phosphorylation mediated by protein kinases and phosphatases has a central regulatory function in many cellular processes in eukaryotes and prokaryotes. As a result, several diseases caused by imbalance in phosphorylation levels are known, especially due to protein tyrosine phosphatases (PTPs) activity, an important family of signaling enzymes. Furthermore, over the last decades several studies have shown the main role of PTPs in pathogenic bacteria: they are associated with growth, cell division, cell wall biosynthesis, biofilm formation, metabolic processes, as well as virulence factor. In this way, PTPs have ascended as targets for antibacterial drug design, particularly in view of the antibiotic resistance in pathogenic bacteria, which demands novel therapeutics strategies. Targeting secreted PTPs is an antivirulence strategy to combat the emergence of antimicrobial resistance (AMR). This review focuses on the recent advances in understanding the role of PTPs and the approaches to target them, with an emphasis in Yersinia spp. and Mycobacterium tuberculosis pathogenesis.
蛋白激酶和磷酸酶介导的蛋白磷酸化在真核生物和原核生物的许多细胞过程中具有核心调节作用。因此，已知几种由于磷酸化水平失衡引起的疾病，特别是由于蛋白酪氨酸磷酸酶（PTP）的活性，这是一个重要的信号酶家族。此外，在过去的几十年中，多项研究表明 PTP 在致病菌中的主要作用：它们与生长、细胞分裂、细胞壁生物合成、生物膜形成、代谢过程以及毒力因子有关。因此，PTP 已成为抗菌药物设计的靶标，特别是考虑到致病菌的抗生素耐药性，这需要新的治疗策略。针对分泌型 PTP 的靶向治疗是一种抗微生物耐药性（AMR）的抗毒力策略。本综述重点介绍了对 PTP 作用及其靶向方法的最新认识进展，特别强调了耶尔森氏菌和结核分枝杆菌发病机制。
