Attachment of ubiquitin molecules to protein substrates is a reversible post-translational modification (PTM), which occurs ubiquitously in eukaryotic cells and controls most cellular processes. As a consequence, ubiquitination is an attractive target of pathogen-encoded virulence factors. Pathogenic bacteria have evolved multiple mechanisms to hijack the host’s ubiquitin system to their advantage. In this review, we discuss the bacteria-encoded E3 ligases and deubiquitinases translocated to the host for an addition or removal of eukaryotic ubiquitin modification, effectively hijacking the host’s ubiquitination processes. We review bacterial enzymes homologous to host proteins in sequence and functions, as well as enzymes with novel mechanisms in ubiquitination, which have significant structural differences in comparison to the mammalian E3 ligases. Finally, we will also discuss examples of molecular “counter-weapons” – eukaryotic proteins, which counteract pathogen-encoded E3 ligases. The many examples of the pathogen effector molecules that catalyze eukaryotic ubiquitin modification bring to light the intricate pathways involved in the pathogenesis of some of the most virulent bacterial infections with human pathogens. The role of these effector molecules remains an essential determinant of bacterial virulence in terms of infection, invasion, and replication. A comprehensive understanding of the mechanisms dictating the mimicry employed by bacterial pathogens is of vital importance in developing new strategies for therapeutic approaches.

泛素分子与蛋白质底物的附着是一种可逆的翻译后修饰 (PTM)，它普遍存在于真核细胞中并控制大多数细胞过程。因此，泛素化是病原体编码毒力因子的一个有吸引力的目标。致病细菌已经进化出多种机制来劫持宿主的泛素系统以发挥其优势。在这篇综述中，我们讨论了细菌编码的 E3 连接酶和去泛素酶转位至宿主，以添加或去除真核泛素修饰，从而有效劫持宿主的泛素化过程。我们回顾了在序列和功能上与宿主蛋白同源的细菌酶，以及具有新的泛素化机制的酶，这些酶与哺乳动物 E3 连接酶相比具有显着的结构差异。最后，我们还将讨论分子“反武器”的例子——真核蛋白，它可以对抗病原体编码的 E3 连接酶。催化真核泛素修饰的病原体效应分子的许多例子揭示了人类病原体的一些最致命的细菌感染的发病机制中涉及的复杂途径。这些效应分子的作用仍然是细菌感染、侵袭和复制毒力的重要决定因素。全面了解细菌病原体拟态的机制对于制定新的治疗策略至关重要。