Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence
Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence
复制标题
DOI：
10.4161/viru.2.2.15039
复制
发表时间：
2011-03-01
期刊：
影响因子：
5.2
通讯作者：
Navarre, William Wiley
中科院分区：
文献类型：
--
作者：
Zou, S. Betty;Roy, Herve;Navarre, William Wiley
细菌病原体检测并整合多种环境信号，协调基因表达的适当变化，包括毒力因子的选择性表达、代谢的变化和应激反应系统的激活。破坏病原体对外部信号反应能力的突变通常是衰减的。在这里，我们讨论了我们最近发现的一种新的转录后调控途径，对沙门氏菌的毒力和抗逆性至关重要。酶PoxA和YjeK协调地将一个独特的β氨基酸连接到翻译因子延伸因子P （EF-P）中高度保守的赖氨酸残基上。由于缺乏PoxA或YjeK而未修饰EF-P的菌株的毒力减弱，并表现出高度多效表型，包括对多种不相关的抗菌化合物的超敏感。我们的实验室和其他人的工作现在表明，以前被认为是必不可少的EF-P，而是通过调节相对有限的蛋白质子集的合成而在翻译中起辅助作用。其他观察结果表明，EF-P的真核同源物eIF5A可能在胁迫适应过程中导致翻译机制发生类似的变化，这表明这些因子在生理学中的作用可能广泛保守。
Bacterial pathogens detect and integrate multiple environmental signals to coordinate appropriate changes in gene expression including the selective expression of virulence factors, changes to metabolism and the activation of stress response systems. Mutations that abolish the ability of the pathogen to respond to external cues are typically attenuating. Here we discuss our recent discovery of a novel post-transcriptional regulatory pathway critical for Salmonella virulence and stress resistance. The enzymes PoxA and YjeK coordinately attach a unique beta-amino acid onto a highly conserved lysine residue in the translation factor elongation factor P (EF-P). Strains in which EF-P is unmodified due to the absence of PoxA or YjeK are attenuated for virulence and display highly pleiotropic phenotypes, including hypersusceptibility to a wide range of unrelated antimicrobial compounds. Work from our laboratory and others now suggests that EF-P, previously thought to be essential, instead plays an ancillary role in translation by regulating the synthesis of a relatively limited subset of proteins. Other observations suggest that the eukaryotic homolog of EF-P, eIF5A, may illicit similar changes in the translation machinery during stress adaptation, indicating that the role of these factors in physiology may be broadly conserved.