Department of Microbiology, University of Illinois at Urbana-Champaigngrid.35403.31, Urbana, Illinois, USA.
J Bacteriol. 2022 Jan 18;204(1):e0037821. doi: 10.1128/JB.00378-21. Epub 2021 Oct 25.
Salmonella enterica serovar Typhimurium invades the intestinal epithelium and induces inflammatory diarrhea using the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS). Expression of the SPI1 T3SS is controlled by three AraC-like regulators, HilD, HilC, and RtsA, which form a feed-forward regulatory loop that leads to activation of , encoding the main transcriptional regulator of the T3SS structural genes. This complex system is affected by numerous regulatory proteins and environmental signals, many of which act at the level of mRNA translation or HilD protein function. Here, we show that the sRNA MicC blocks translation of the mRNA by base pairing near the ribosome binding site. MicC does not induce degradation of the message. Our data indicate that is transcriptionally activated by SlyA, and SlyA feeds into the SPI1 regulatory network solely through MicC. Transcription of is negatively regulated by the OmpR/EnvZ two-component system, but this regulation is dependent on SlyA. OmpR/EnvZ control SPI1 expression partially through MicC but also affect expression through other pathways, including an EnvZ-dependent, OmpR-independent mechanism. MicC-mediated regulation plays a role during infection, as evidenced by an SPI1 T3SS-dependent increase in Salmonella fitness in the intestine in the deletion mutant. These results further elucidate the complex regulatory network controlling SPI1 expression and add to the list of sRNAs that control this primary virulence factor. The Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS) is the primary virulence factor required for causing intestinal disease and initiating systemic infection. The system is regulated in response to a large variety of environmental and physiological factors such that the T3SS is expressed at only the appropriate time and place in the host during infection. Here, we show how the sRNA MicC affects expression of the system. This work adds to our detailed mechanistic studies aimed at a complete understanding of the regulatory circuit.
鼠伤寒沙门氏菌血清型 Typhimurium 通过沙门氏菌致病性岛 1（SPI1）III 型分泌系统（T3SS）入侵肠道上皮并引发炎症性腹泻。SPI1 T3SS 的表达受三个 AraC 样调控因子 HilD、HilC 和 RtsA 控制，它们形成一个正反馈调控环，导致编码 T3SS 结构基因主要转录调控因子的 基因的激活。这个复杂的系统受到许多调节蛋白和环境信号的影响，其中许多作用于 mRNA 翻译或 HilD 蛋白功能的水平。在这里，我们表明，sRNA MicC 通过与核糖体结合位点附近的碱基配对来阻断 mRNA 的翻译。MicC 不会诱导 消息的降解。我们的数据表明， 基因转录被 SlyA 激活，而 SlyA 通过 MicC 仅作用于 SPI1 调控网络。 基因的转录受 OmpR/EnvZ 双组分系统的负调控，但这种调控依赖于 SlyA。OmpR/EnvZ 通过 MicC 部分控制 SPI1 的表达，但也通过其他途径影响表达，包括一种依赖于 EnvZ 的、不依赖于 OmpR 的机制。MicC 介导的调控在感染过程中发挥作用，这可以从 SPI1 T3SS 缺失突变在肠道中导致沙门氏菌适应性增加这一事实中得到证明。这些结果进一步阐明了控制 SPI1 表达的复杂调控网络，并增加了控制这一主要毒力因子的 sRNA 列表。 沙门氏菌致病性岛 1（SPI1）III 型分泌系统（T3SS）是引起肠道疾病和启动全身感染所必需的主要毒力因子。该系统受到大量环境和生理因素的调节，以便在感染过程中仅在宿主的适当时间和地点表达 T3SS。在这里，我们展示了 sRNA MicC 如何影响该系统的表达。这项工作增加了我们对旨在全面了解调控回路的详细机制研究。
