Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.
Int J Mol Sci. 2022 Jan 8;23(2):670. doi: 10.3390/ijms23020670.
Inorganic polyphosphate (polyP) has been implicated in an astonishing array of biological functions, ranging from phosphorus storage to molecular chaperone activity to bacterial virulence. In bacteria, polyP is synthesized by polyphosphate kinase (PPK) enzymes, which are broadly subdivided into two families: PPK1 and PPK2. While both enzyme families are capable of catalyzing polyP synthesis, PPK1s preferentially synthesize polyP from nucleoside triphosphates, and PPK2s preferentially consume polyP to phosphorylate nucleoside mono- or diphosphates. Importantly, many pathogenic bacteria such as and encode at least one of each PPK1 and PPK2, suggesting these enzymes may be attractive targets for antibacterial drugs. Although the majority of bacterial polyP studies to date have focused on PPK1s, PPK2 enzymes have also begun to emerge as important regulators of bacterial physiology and downstream virulence. In this review, we specifically examine the contributions of PPK2s to bacterial polyP homeostasis. Beginning with a survey of the structures and functions of biochemically characterized PPK2s, we summarize the roles of PPK2s in the bacterial cell, with a particular emphasis on virulence phenotypes. Furthermore, we outline recent progress on developing drugs that inhibit PPK2 enzymes and discuss this strategy as a novel means of combatting bacterial infections.
无机多聚磷酸盐（polyP）在许多生物学功能中发挥了重要作用，范围从磷储存到分子伴侣活性到细菌毒力。在细菌中，多聚磷酸盐由多聚磷酸盐激酶（PPK）酶合成，这些酶广泛分为两类：PPK1 和 PPK2。虽然这两种酶家族都能够催化多聚磷酸盐的合成，但 PPK1 优先从核苷三磷酸合成多聚磷酸盐，而 PPK2 优先消耗多聚磷酸盐来磷酸化核苷单或二磷酸。重要的是，许多致病菌，如 和 ，至少编码一种 PPK1 和 PPK2，这表明这些酶可能是抗菌药物的有吸引力的靶标。尽管迄今为止大多数细菌多聚磷酸盐研究都集中在 PPK1 上，但 PPK2 酶也开始成为细菌生理学和下游毒力的重要调节剂。在这篇综述中，我们特别研究了 PPK2 对细菌多聚磷酸盐稳态的贡献。首先调查了生化特征明确的 PPK2 的结构和功能，我们总结了 PPK2 在细菌细胞中的作用，特别强调了毒力表型。此外，我们概述了最近在开发抑制 PPK2 酶的药物方面的进展，并讨论了将其作为对抗细菌感染的新策略的潜力。
