Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, L8S 4L8, Canada.
Departamento de Microbiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
Cell Rep. 2018 Oct 23;25(4):825-832.e5. doi: 10.1016/j.celrep.2018.09.078.
Bacterial two-component regulatory systems (TCS) couple the detection of niche-specific cues with adaptive gene expression to optimize fitness. In Salmonella Typhimurium (STM), the SsrA-SsrB TCS regulates virulence genes needed for survival within host cells, yet the impact of this TCS on regulatory evolution in this pathogen remains incompletely understood. Here, we show that SsrB alters a transcriptional network controlling bacterial motility to limit inflammasome activation during host cell infection. Using comparative RNA sequencing between STM and S. bongori (SBG) engineered to express SsrB, we show that SsrB represses flagellar gene expression in STM but activates this pathway in SBG, which has evolved in the absence of SsrB. Motility repression in STM is driven by an SsrB-binding region upstream of flhDC that appears to have evolved in STM following divergence from SBG. These data reveal a divergent regulatory circuit in non-coding DNA that reduces flagellar gene expression to evade host defenses.
细菌双组分调控系统 (TCS) 将特定生态位线索的检测与适应性基因表达相耦合，以优化适应性。在鼠伤寒沙门氏菌 (STM) 中，SsrA-SsrB TCS 调节了在宿主细胞内存活所需的毒力基因，然而，该 TCS 对该病原体中调控进化的影响仍不完全清楚。在这里，我们表明 SsrB 改变了一个控制细菌运动性的转录网络，以限制宿主细胞感染期间的炎症小体激活。我们使用在表达 SsrB 的 STM 和 S. bongori (SBG) 之间进行的比较 RNA 测序表明，SsrB 在 STM 中抑制了鞭毛基因的表达，但在 SBG 中激活了该途径，SBG 在没有 SsrB 的情况下进化而来。STM 中的运动性抑制是由 flhDC 上游的 SsrB 结合区域驱动的，该区域似乎在 STM 从 SBG 分化后进化而来。这些数据揭示了非编码 DNA 中一个不同的调控回路，该回路降低了鞭毛基因的表达，以逃避宿主防御。
