摘要：对代谢通路的重编程是病原体在致命环境中存活的关键。在此，我们揭示了沙门氏菌在翻译水平上快速响应外部环境的机制：即核糖体蛋白S1的K247位点动态乙酰化修饰可调控不同mRNA的翻译，以适应不同的感染阶段。我们发现，非乙酰化的S1K247优先招募与鞭毛组装、硫代谢

期刊导读

Journal Guide

1

Reversible acetylation of ribosomal protein S1 serves as a smart switch for Salmonella to rapidly adapt to host stress

对代谢通路的重编程是病原体在致命环境中存活的关键。在此，我们揭示了沙门氏菌在翻译水平上快速响应外部环境的机制：即核糖体蛋白S1的K247位点动态乙酰化修饰可调控不同mRNA的翻译，以适应不同的感染阶段。我们发现，非乙酰化的S1K247优先招募与鞭毛组装、硫代谢和SPI-1型三型分泌系统（T3SS）相关的mRNA；相反，由Pat酶催化的S1K247乙酰化形式则倾向于结合精氨酸生物合成相关mRNA，从而激活调控SPI-2毒力因子的转录因子ArgR，使沙门氏菌能够在巨噬细胞内存活和复制。值得注意的是，K247乙酰化模拟突变株在离体和体内实验中均表现出更强的毒力。这一机制不仅有助于深入理解病原体在复杂环境中的存活策略，也为鉴定消除病原菌的新靶点和新通路提供了方向。

（信息以英文摘要为准）

2

文章介绍：

近日，生物工程学院、生物反应器工程全国重点实验室叶邦策教授团队在翻译后修饰调控病原微生物致病机理领域取得重要进展，相关成果以“Reversible Acetylation of Ribosomal Protein S1 Serves as a Smart Switch for Salmonella to Rapidly Adapt to Host Stress”为题，发表于国际核酸研究领域权威期刊Nucleic Acids Research。

沙门氏菌（Salmonella）作为典型的食源性胞内致病菌，其致病性依赖于对宿主细胞内复杂环境的快速感知与适应性调控能力。在应对环境压力时，不仅依赖双组分系统介导的转录调控，还可通过翻译水平的动态调控实现更快速的应激响应。目前，关于原核生物如何通过翻译后修饰介导的核糖体异质性来调控蛋白质合成，并进而影响其致病能力的分子机制，仍缺乏明确证据。

在该研究中揭示了一种新型的细菌毒力调控机制：鼠伤寒沙门氏菌通过动态调控核糖体蛋白S1的K247可逆乙酰化状态，实现翻译程序的精确重编程，从而适应宿主不同感染阶段的环境压力。研究证实，K247乙酰化由乙酰转移酶Pat和去乙酰化酶CobB动态调控。通过核糖体-新生肽链测序技术（RNC-Seq）分析，发现K247非酰基化状态倾向于结合鞭毛组装、硫代谢及SPI-1 T3SS相关mRNA，促进细菌早期侵袭能力；K247乙酰化则偏好性招募精氨酸合成及SPI-2相关mRNA，其中L-精氨酸可通过激活调控蛋白ArgR进一步上调SPI-2毒力因子的表达，从而增强细菌在巨噬细胞内的存活与复制能力。这一机制的发掘不仅阐明了病原菌利用翻译调控优化毒力表达的分子机制，也为开发针对核糖体翻译调控的新型抗菌策略提供了潜在靶点。

博士生沈奕琳为该论文第一作者，周英教授和叶邦策教授为共同通讯作者。该研究得到了国家重点研发计划和国家自然科学基金重点项目的支持。

期刊介绍

《核酸研究》（Nucleic Acids Research）是在1974年创刊，由牛津大学出版社经过同行评审公开出版的科学期刊。核酸研究（NAR）出版在物理，化学，生物化学和生物学方面有关核酸，和与核酸代谢和/或相互作用相关的蛋白质的前沿研究成果。

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Looking back at 20 years of Open Access publishing at Nucleic Acids Research

Precision genome editing and in-cell measurements of oxidative DNA damage repair enable functional and mechanistic characterization of cancer-associated MUTYH variants

Exploring the relationship between aptamer binding thermodynamics, affinity, and specificity

Mapping small molecule–RNA binding sites via Chem-CLIP synergized with capillary electrophoresis and nanopore sequencing

Next generation APOBEC3 inhibitors: optimally designed for potency and nuclease stability

Template-independent enzymatic functionalization of DNA oligonucleotides with environment-sensitive nucleotide probes using terminal deoxynucleotidyl transferase

Oxidative events in a double helix system promote the formation of kinetically trapped G-quadruplexes

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