University of Texas Southwestern Medical Center, Department of Microbiology, Dallas, TX 75390-9048, USA.
Infect Immun. 2010 Mar;78(3):914-26. doi: 10.1128/IAI.01038-09. Epub 2009 Dec 22.
The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system mediates chemical communication between bacteria and their mammalian hosts. The three signals are sensed by the QseC histidine kinase (HK) sensor. Salmonella enterica serovar Typhimurium is a pathogen that uses HKs to sense its environment and regulate virulence. Salmonella serovar Typhimurium invades epithelial cells and survives within macrophages. Invasion of epithelial cells is mediated by the type III secretion system (T3SS) encoded in Salmonella pathogenicity island 1 (SPI-1), while macrophage survival and systemic disease are mediated by the T3SS encoded in SPI-2. Here we show that QseC plays an important role in Salmonella serovar Typhimurium pathogenicity. A qseC mutant was impaired in flagellar motility, in invasion of epithelial cells, and in survival within macrophages and was attenuated for systemic infection in 129x1/SvJ mice. QseC acts globally, regulating expression of genes within SPI-1 and SPI-2 in vitro and in vivo (during infection of mice). Additionally, dopamine beta-hydroxylase knockout (Dbh(-)(/)(-)) mice that do not produce Epi or NE showed different susceptibility to Salmonella serovar Typhimurium infection than wild-type mice. These data suggest that the AI-3/Epi/NE signaling system is a key factor during Salmonella serovar Typhimurium pathogenesis in vitro and in vivo. Elucidation of the role of this interkingdom signaling system in Salmonella serovar Typhimurium should contribute to a better understanding of the complex interplay between the pathogen and the host during infection.
自动诱导物-3 (AI-3)/肾上腺素 (Epi)/去甲肾上腺素 (NE) 种间信号系统介导细菌与其哺乳动物宿主之间的化学通讯。这三种信号由 QseC 组氨酸激酶 (HK) 传感器感知。鼠伤寒沙门氏菌是一种利用 HKs 感知其环境并调节毒力的病原体。鼠伤寒沙门氏菌侵袭上皮细胞并在巨噬细胞内存活。上皮细胞的侵袭由沙门氏菌致病岛 1 (SPI-1) 编码的 III 型分泌系统 (T3SS) 介导，而巨噬细胞的存活和全身性疾病则由 SPI-2 编码的 T3SS 介导。在这里，我们表明 QseC 在鼠伤寒沙门氏菌致病性中起着重要作用。qseC 突变体在鞭毛运动、上皮细胞侵袭和巨噬细胞内存活方面受损，并且在 129x1/SvJ 小鼠中系统性感染的能力减弱。QseC 具有全局作用，在体外和体内 (在感染小鼠期间) 调节 SPI-1 和 SPI-2 内基因的表达。此外，不产生 Epi 或 NE 的多巴胺-β-羟化酶敲除 (Dbh(-)(/)(-)) 小鼠对鼠伤寒沙门氏菌感染的敏感性与野生型小鼠不同。这些数据表明，AI-3/Epi/NE 信号系统是鼠伤寒沙门氏菌体外和体内发病机制的关键因素。阐明这种种间信号系统在鼠伤寒沙门氏菌中的作用应有助于更好地理解感染过程中病原体和宿主之间的复杂相互作用。
