Department of Biochemistry, Indian Institute of Science, Bangalore, India.
FEBS Lett. 2024 Jul;598(13):1605-1619. doi: 10.1002/1873-3468.14853. Epub 2024 Mar 19.
Salmonella Typhimurium is an enteric pathogen that is highly tolerant to bile. Next-generation mRNA sequencing was performed to analyze the adaptive responses to bile in two S. Typhimurium strains: wild type (WT) and a mutant lacking cold shock protein E (ΔcspE). CspE is an RNA chaperone which is crucial for survival of S. Typhimurium during bile stress. This study identifies transcriptional responses in bile-tolerant WT and bile-sensitive ΔcspE. Upregulation of several genes involved in nitrate metabolism was observed, including fnr, a global regulator of nitrate metabolism. Notably, Δfnr was susceptible to bile stress. Also, complementation with fnr lowered reactive oxygen species and enhanced the survival of bile-sensitive ΔcspE. Importantly, intracellular nitrite amounts were highly induced in bile-treated WT compared to ΔcspE. Also, the WT strain pre-treated with nitrate displayed better growth with bile. These results demonstrate that nitrate-dependent metabolism promotes adaptation of S. Typhimurium to bile.
鼠伤寒沙门氏菌是一种肠道病原体，对胆盐有很强的耐受性。本研究采用下一代 mRNA 测序分析了两种鼠伤寒沙门氏菌（野生型（WT）和缺乏冷休克蛋白 E（ΔcspE）突变体）对胆盐的适应性反应。CspE 是一种 RNA 伴侣，对鼠伤寒沙门氏菌在胆盐应激下的存活至关重要。本研究鉴定了耐胆盐的 WT 和胆盐敏感的 ΔcspE 的转录反应。观察到参与硝酸盐代谢的几个基因的上调，包括 fnr，硝酸盐代谢的全局调节剂。值得注意的是，Δfnr 易受胆盐应激的影响。此外，用 fnr 进行互补降低了活性氧并增强了胆盐敏感的 ΔcspE 的存活。重要的是，与 ΔcspE 相比，胆盐处理的 WT 细胞内亚硝酸盐含量显著增加。此外，用硝酸盐预处理的 WT 菌株在胆盐中生长更好。这些结果表明，硝酸盐依赖的代谢促进了鼠伤寒沙门氏菌对胆盐的适应。
