Pseudomonas aeruginosa cleaves the decoding center of Caenorhabditis elegans ribosomes.
Pseudomonas aeruginosa cleaves the decoding center of Caenorhabditis elegans ribosomes.
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DOI：
10.1371/journal.pbio.3000969
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发表时间：
2020-12
期刊：
影响因子：
9.8
通讯作者：
Ambros V
中科院分区：
文献类型：
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作者：
Vasquez-Rifo A;Ricci EP;Ambros V
病原体如铜绿假单胞菌有利地改变动物宿主生理，例如，通过抑制宿主蛋白质合成。铜绿假单胞菌对昆虫和哺乳动物宿主的翻译抑制利用了众所周知的外毒素A效应物。然而，对于铜绿假单胞菌（P. aeruginosa）感染秀丽隐杆线虫，其翻译抑制的确切途径和机制尚不清楚。我们发现，当暴露于P. aeruginosa PA14时，秀丽隐杆线虫经历了完整核糖体的快速损失，并伴随着核糖体解码中心关键部分26S核糖体RNA （rRNA）的螺旋69 （H69）切割的核糖体的积累。某些毒力强的P. aeruginosa分离物以群体感应（QS）依赖的方式诱导H69裂解，独立于外毒素a介导的翻译抑制。H69的分裂被pmk-1、fshr1和zip2基因定义的3种主要宿主防御途径所拮抗。H69的裂解水平随着细菌暴露时间的增加而增加，并且主要局限于蠕虫的肠道组织。遗传和基因组分析表明，H69的切割导致了蠕虫zip-2介导的防御反应途径的激活，与翻译抑制一致。综上所述，我们的观察结果表明，铜绿假单胞菌具有诱导核糖体降解和宿主核糖体H69裂解的毒力机制。通过这种方式，铜绿假单胞菌会破坏宿主翻译并阻断抗菌反应。在铜绿假单胞菌感染秀丽隐杆线虫的过程中，细菌的毒力机制导致宿主核糖体rna在解码中心切割，从而关闭翻译。
Pathogens such as Pseudomonas aeruginosa advantageously modify animal host physiology, for example, by inhibiting host protein synthesis. Translational inhibition of insects and mammalian hosts by P. aeruginosa utilizes the well-known exotoxin A effector. However, for the infection of Caenorhabditis elegans by P. aeruginosa, the precise pathways and mechanism(s) of translational inhibition are not well understood. We found that upon exposure to P. aeruginosa PA14, C. elegans undergoes a rapid loss of intact ribosomes accompanied by the accumulation of ribosomes cleaved at helix 69 (H69) of the 26S ribosomal RNA (rRNA), a key part of ribosome decoding center. H69 cleavage is elicited by certain virulent P. aeruginosa isolates in a quorum sensing (QS)–dependent manner and independently of exotoxin A–mediated translational repression. H69 cleavage is antagonized by the 3 major host defense pathways defined by the pmk-1, fshr-1, and zip-2 genes. The level of H69 cleavage increases with the bacterial exposure time, and it is predominantly localized in the worm’s intestinal tissue. Genetic and genomic analysis suggests that H69 cleavage leads to the activation of the worm’s zip-2-mediated defense response pathway, consistent with translational inhibition. Taken together, our observations suggest that P. aeruginosa deploys a virulence mechanism to induce ribosome degradation and H69 cleavage of host ribosomes. In this manner, P. aeruginosa would impair host translation and block antibacterial responses. During infection of the nematode Caenorhabditis elegans by the bacterium Pseudomonas aeruginosa, a bacterial virulence mechanism leads to the cleavage of host ribosomal RNAs at the decoding center, thereby shutting down translation.
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