Srikanth Chittur V, Verma Smriti
Regional Centre for Biotechnology, NCR Biotech Science Cluster, 3rd Milestone, Gurgaon Faridabad Expressway, Bhankri Village, Faridabad, Haryana, India.
Mucosal Immunology Lab, Massachusetts General Hospital, Building 114, Charlestown, MA, USA.
Adv Exp Med Biol. 2017;963:389-408. doi: 10.1007/978-3-319-50044-7_22.
Post translational modification pathways regulate fundamental processes of cells and thus govern vital functions. Among these, particularly the modification with Small Ubiquitin-like Modifiers (SUMO) is being recognized as a pathway crucial for cell homeostasis and health. Understandably, bacterial pathogens intervene with the SUMO pathway of the host for ensuring successful infection. Among the bacterial pathogens known to target host sumoylation varied points of intervention are utilized. Majority of them including Salmonella Typhimurium, Shigella flexneri and Listeria monocytogenes target the E2 conjugating enzyme Ubc9. While others, such as Xanthomonase compestris, target the desumoylation machineries mimicking cysteine protease activity. Still others such as Ehrlichia chaffeensis and Anaplasma phagocytophilum utilize host SUMO-machinery for sumoylating their own effectors. Together such changes lead to modulation of host proteome and transcriptome thereby leading to major alterations in signal transduction that favor invasion and bacterial multiplication. Such interplay between bacterial pathogens and host sumoylation has added a new dimension to host-pathogen biology and its understanding could be vital for developing potential therapeutic intervention strategies.
翻译后修饰途径调节细胞的基本过程,从而控制重要功能。其中,特别是小泛素样修饰物(SUMO)的修饰被认为是细胞稳态和健康的关键途径。可以理解的是,细菌病原体干预宿主的SUMO途径以确保成功感染。在已知靶向宿主SUMO化的细菌病原体中,采用了不同的干预点。其中大多数,包括鼠伤寒沙门氏菌、福氏志贺氏菌和单核细胞增生李斯特菌,靶向E2缀合酶Ubc9。而其他一些细菌,如野油菜黄单胞菌,则靶向模拟半胱氨酸蛋白酶活性的去SUMO化机制。还有一些细菌,如恰菲埃立克体和嗜吞噬细胞无形体,利用宿主的SUMO机制对自身效应器进行SUMO化。这些变化共同导致宿主蛋白质组和转录组的调节,从而导致信号转导的重大改变,有利于入侵和细菌繁殖。细菌病原体与宿主SUMO化之间的这种相互作用为宿主-病原体生物学增添了新的维度,对其的理解对于开发潜在的治疗干预策略可能至关重要。