Mutations in the Escherichia coli ribosomal protein L22 selectively suppress the expression of a secreted bacterial virulence factor.
Mutations in the Escherichia coli ribosomal protein L22 selectively suppress the expression of a secreted bacterial virulence factor.
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大肠杆菌核糖体蛋白 L22 的突变选择性抑制分泌的细菌毒力因子的表达。
DOI：
10.1128/jb.00211-13
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发表时间：
2013
影响因子：
3.2
通讯作者：
Bernstein,HarrisD
中科院分区：
文献类型：
--
作者：
Yap,Mee-NganF;Bernstein,HarrisD
在大肠杆菌中损害肽介导的翻译停滞的核糖体蛋白L22中的突变已被证明会减少几个基因的表达，包括secA，其编码通过Sec途径驱动蛋白质输出的ATP酶。在这里，我们使用比较蛋白质组学方法来深入了解L22（Δ82-84）突变对基因表达和蛋白质合成的整体影响。虽然该突变没有影响或适度影响大多数可溶性蛋白的水平，但它显著降低了抗原43（Ag 43）的水平，这是一种促进自聚集的分泌型毒力因子。蛋白浓度的降低与Ag 43 mRNA的丰度和稳定性的急剧下降相关。我们发现secA的过表达或编码分泌前蛋白和膜蛋白的基因的失活恢复了L22突变株中Ag 43的产生。此外，在野生型菌株的Sec途径的损害减少了Ag 43的生产，但没有显着影响其他prerecretory蛋白的合成。综上所述，这些结果表明，Ag 43基因的表达是非常敏感的Sec机制的状态，并强烈表明，L22突变降低Ag 43浓度间接降低secA表达。我们的研究结果意味着存在一种新的调节机制，其中蛋白质出口的效率与基因表达相结合，并有助于解释已观察到的分泌应激对SecA合成的调节。
Mutations in the ribosomal protein L22 that impair peptide-mediated translation arrest in Escherichia coli have been shown to reduce the expression of several genes, includingsecA, which encodes an ATPase that drives protein export via the Sec pathway. Here, we used a comparative proteomic approach to obtain insight into the global effects of the L22(Δ82-84) mutation on gene expression and protein synthesis. While the mutation did not affect or modestly affected the level of most soluble proteins, it dramatically reduced the level of antigen 43 (Ag43), a secreted virulence factor that promotes autoaggregation. The reduced protein concentration correlated with a sharp decrease in the abundance and stability of Ag43 mRNA. We found that the overexpression ofsecAor the inactivation of genes that encode presecretory and membrane proteins restored Ag43 production in the L22 mutant strain. Furthermore, impairment of the Sec pathway in a wild-type strain reduced Ag43 production but did not significantly affect the synthesis of other presecretory proteins. Taken together, these results indicate that Ag43 gene expression is exquisitely sensitive to the status of the Sec machinery and strongly suggest that the L22 mutation decreases the Ag43 concentration indirectly by reducingsecAexpression. Our results imply the existence of a novel regulatory mechanism in which the efficiency of protein export is coupled to gene expression and help to explain the modulation of SecA synthesis that has been observed in response to secretion stress.